Publications

Science Advances

2020 Apr 29;6(18):eaaz8822. doi: 10.1126/sciadv.aaz8822. 

Benhaim MA, Mangala Prasad V, Garcia NK, Guttman M, Lee KK

The influenza virus hemagglutinin (HA) fusion protein has long been viewed as a "spring-loaded" fusion machine whereby activation at low pH initiates a rapid and irreversible cascade of conformational changes that drives the membrane fusion reaction. This mechanism has shaped our understanding of how type 1 viral fusion proteins function as a whole. Experimental limitations have hindered efforts to expand our mechanistic and structural understanding of viral membrane fusion. Here, we used pulse-labeling hydrogen/deuterium exchange mass spectrometry and cryo-electron tomography to monitor and characterize the structural dynamics of HA during fusion activation on intact virions. Our data reveal how concurrent reorganizations at the HA1 receptor binding domain interface and HA2 fusion subunit produce a dynamic fusion intermediate ensemble in full-length HA. The soluble HA ectodomain transitions directly to the postfusion state with no observable intermediate.

Benhaim_SciAdv_2020_Fig.png

Why Do We Act Like This?

Journal of Virology
2018
Feb 26;92(6):e02006-17. doi: 10.1128/JVI.02006-17.
Williams JA, Gui L, Hom N, Mileant A, Lee KK

The influenza virus hemagglutinin (HA) fusion glycoprotein mediates entry into target cells and is the primary antigenic target of neutralizing antibod- ies (nAbs). Our current structural understanding of mechanisms of antibody (Ab)- mediated neutralization largely relies on the high-resolution characterization of anti- gen binding (Fab) fragments in complex with soluble, isolated antigen constructs by cryo-electron microscopy (EM) single-particle reconstruction or X-ray crystallography. Interactions between full-length IgG and whole virions have not been well character- ized, and a gap remains in our understanding of how intact Abs neutralize virus and prevent infection. Using structural and biophysical approaches, we observed that Ab-mediated inhibition of HA function and neutralization of virus infectivity occur by multiple coexisting mechanisms, are largely dependent on the specific epitope that is targeted, and are highly dependent on the bivalent nature of IgG molecules.

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eLife
2021 Jul 15;10:e68110. doi: 10.7554/eLife.68110.
Shipley MM, Mangala Prasad V, Doepker LE, Dingens AS, Ralph DK, Harkins E, Dhar A, Arenz D, Chohan V, Weight H, Mandaliya K, Bloom JD, Matsen Iv F, Lee KK, Overbaugh JM.

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV-1 superinfection elicits broad nAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. Mature bnAb QA013.2 bound both initial transmitted and superinfecting virus, but its inferred naïve bound only the superinfecting strain and was not neutralizing. QA013.2 requires residues spanning FWRH1-CDRH1 to attain breadth, which is uncommon for V3-specific bnAbs. A 4.15 Å cryo-EM structure of QA013.2 bound to heterologous native-like trimer showed recognition of V3 signatures (N301, N332, and GDIR). Antigenic profiling revealed that viral escape was achieved not only by changes in the structurally-defined epitope, but also by mutations in V1. These results highlight shared and distinct properties of QA013.2 relative to other V3-specific bnAbs in the setting of sequential, diverse antigenic variants.

QA013.1_Fig.png

Journal of Virology

2016 Jul 11;90(15):6948-6962. doi: 10.1128/JVI.00240-16.

Gui L, Ebner JL, Mileant A, Williams JA, Lee KK.

Enveloped viruses employ specialized surface proteins to mediate fusion of cellular and viral membranes that results in the formation of pores through which the viral genetic material is delivered to the cell. For influenza virus, the trimeric hemagglutinin (HA) glycoprotein spike mediates host cell attachment and membrane fusion. While structures of a subset of conformations and parts of the fusion machinery have been characterized, the nature and sequence of membrane deformations during fusion have largely eluded characterization. Building upon studies that focused on early stages of HA-mediated membrane remodeling, here cryo-electron tomography (cryo-ET) was used to image the three-dimensional organization of intact influenza virions at different stages of fusion with liposomes, leading all the way to completion of the fusion reaction. By monitoring the evolution of fusion intermediate populations over the course of acid-induced fusion, we identified the progression of membrane reorganization that leads to efficient fusion by an enveloped virus.

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OUR ARTICLES

Please see Pubmed for current list of publications: https://pubmed.ncbi.nlm.nih.gov/?term=kelly+k+lee&sort=date

2021

 

Stabilization of the SARS-CoV-2 Spike Receptor-Binding Domain Using Deep Mutational Scanning and Structure-Based Design.

Ellis D, Brunette N, Crawford KHD, Walls AC, Pham MN, Chen C, Herpoldt KL, Fiala B, Murphy M, Pettie D, Kraft JC, Malone KD, Navarro MJ, Ogohara C, Kepl E, Ravichandran R, Sydeman C, Ahlrichs M, Johnson M, Blackstone A, Carter L, Starr TN, Greaney AJ, Lee KK, Veesler D, Bloom JD, King NP.

Front Immunol. 2021 Jun 29;12:710263. doi: 10.3389/fimmu.2021.710263. 

Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection.

Shipley MM*, Mangala Prasad V*, Doepker LE, Dingens AS, Ralph DK, Harkins E, Dhar A, Arenz D, Chohan V, Weight H, Mandaliya K, Bloom JD, Matsen Iv F, Lee KK†, Overbaugh JM†.

Elife. 2021 Jul 15;10:e68110. doi: 10.7554/eLife.68110. 

 

Quadrivalent influenza nanoparticle vaccines induce broad protection.

Boyoglu-Barnum S, Ellis D, Gillespie RA, Hutchinson GB, Park Y-J, Moi SM, Acton OJ, Ravichandran R, Murphy M, Pettie D, Matheson N, Carter L, Creanga A, Watson MJ, Kephart S, Ataca S, Vaile JR, Ueda G, Crank M, Stewart L, Lee KK, Guttman M, Baker D, Mascola JR, Veesler D, Graham BS, King NP, Kanekiyo M. 

Nature 2021 Mar 24; 10.1038/s41586-021-03365-x. 

 

Development of antibody-dependent cell cytotoxicity function in HIV-1 antibodies.

Doepker LE, Danon S, Harkins E, Ralph DK, Yaffe Z, Garrett ME, Dhar A, Wagner C, Stumpf MM, Arenz D, Williams JA, Jaoko W, Mandaliya K, Lee KK, Matsen FA 4th, Overbaugh JM. 

Elife. 2021 Jan 11;10:e63444. doi: 10.7554/eLife.63444.

 

Simple Platform for Automating Decoupled LC-MS Analysis of Hydrogen/Deuterium Exchange Samples.

Watson MJ, Harkewicz R, Hodge EA, Vorauer C, Palmer J, Lee KK, Guttman M. 

J Am Soc Mass Spectrom. 2021 Feb 3;32(2):597-600. doi: 10.1021/jasms.0c00341.

 

2020

 

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.

Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, Tse LV, Shehata L, O'Connor MA, Chen C, Navarro MJ, Miranda MC, Pettie D, Ravichandran R, Kraft JC, Ogohara C, Palser A, Chalk S, Lee EC, Guerriero K, Kepl E, Chow CM, Sydeman C, Hodge EA, Brown B, Fuller JT, Dinnon KH 3rd, Gralinski LE, Leist SR, Gully KL, Lewis TB, Guttman M, Chu HY, Lee KK, Fuller DH, Baric RS, Kellam P, Carter L, Pepper M, Sheahan TP, Veesler D, King NP. 

Cell. 2020 Nov 25;183(5):1367-1382.e17. doi: 10.1016/j.cell.2020.10.043. 

 

The influence of proline isomerization on potency and stability of anti-HIV antibody 10E8.

Guttman M, Padte NN, Huang Y, Yu J, Rocklin GJ, Weitzner BD, Scian M, Ho DD, Lee KK. 

Scientific Rep. 2020 Aug 31;10(1):14313. doi: 10.1038/s41598-020-71184-7.

 

Direct imaging of liquid domains in membranes by cryo-electron tomography.

Cornell CE, Mileant A, Thakkar N, Lee KK, Keller SL. 

Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):19713-19719. doi: 10.1073/pnas.2002245117. 

 

Structural monitoring of a transient intermediate in the hemagglutinin fusion machinery on influenza virions.

Benhaim MA, Mangala Prasad V, Garcia NK, Guttman M, Lee KK. 

Science Advances 2020 Apr 29;6(18):eaaz8822. doi: 10.1126/sciadv.aaz8822. 

 

2019

 

Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes.

Cornell CE, Black RA, Xue M, Litz HE, Ramsay A, Gordon M, Mileant A, Cohen ZR, Williams JA, Lee KK, Drobny GP, Keller SL. 

Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17239-17244. doi: 10.1073/pnas.1900275116. 

 

Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage.

Simonich CA, Doepker L, Ralph D, Williams JA, Dhar A, Yaffe Z, Gentles L, Small CT, Oliver B, Vigdorovich V, Mangala Prasad V, Nduati R, Sather DN, Lee KK, Matsen Iv FA, Overbaugh J. 

Nature Commun. 2019 May 16;10(1):2190. doi: 10.1038/s41467-019-09481-7.

 

De novo design of tunable, pH-driven conformational changes.

Boyken SE, Benhaim MA, Busch F, Jia M, Bick MJ, Choi H, Klima JC, Chen Z, Walkey C, Mileant A, Sahasrabuddhe A, Wei KY, Hodge EA, Byron S, Quijano-Rubio A, Sankaran B, King NP, Lippincott-Schwartz J, Wysocki VH, Lee KK, Baker D. 

Science. 2019 May 17;364(6441):658-664. doi: 10.1126/science.aav7897.

 

Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance.

Hom N, Gentles L, Bloom JD, Lee KK. 

J Virol. 2019 Jun 14;93(13):e00161-19. doi: 10.1128/JVI.00161-19.

 

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.

Marcandalli J, Fiala B, Ols S, Perotti M, de van der Schueren W, Snijder J, Hodge E, Benhaim M, Ravichandran R, Carter L, Sheffler W, Brunner L, Lawrenz M, Dubois P, Lanzavecchia A, Sallusto F, Lee KK, Veesler D, Correnti CE, Stewart LJ, Baker D, Loré K, Perez L, King NP. 

Cell. 2019 Mar 7;176(6):1420-1431.e17. doi: 10.1016/j.cell.2019.01.046.

 

2018

 

Influenza Virus-Liposome Fusion Studies Using Fluorescence Dequenching and Cryo-electron Tomography.

Gui L, Lee KK. 

Methods Mol Biol. 2018;1836:261-279. doi: 10.1007/978-1-4939-8678-1_13.

 

Nucleoside-modified mRNA Vaccines Induce Potent T Follicular Helper and Germinal Center B Cell Responses.

Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E, LaBranche CC, Montefiori DC, Lobby JL, Saunders KO, Liao HX, Korber BT, Sutherland LL, Scearce RM, Hraber PT, Tombácz I, Muramatsu H, Ni H, Balikov DA, Li C, Mui BL, Tam YK, Krammer F, Karikó K, Polacino P, Eisenlohr LC, Madden TD, Hope MJ, Lewis MG, Lee KK, Hu SL, Hensley SE, Cancro MP, Haynes BF, Weissman D. 

J Exp Med. 2018 Jun 4;215(6):1571-1588. doi: 10.1084/jem.20171450. 

 

Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire.

Williams KL, Wang B, Arenz D, Williams JA, Dingens AS, Cortez V, Simonich CA, Rainwater S, Lehman DA, Lee KK, Overbaugh J.

Cell Rep. 2018 Apr 17;23(3):682-691. doi: 10.1016/j.celrep.2018.03.082.

 

Dissection of Epitope-Specific Mechanisms of Neutralization of Influenza Virus by Intact IgG and Fab Fragments.

Williams JA, Gui L, Hom N, Mileant A, Lee KK. 

J Virol. 2018 Feb 26;92(6):e02006-17. doi: 10.1128/JVI.02006-17.

 

2017

 

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.

Torrents de la Peña A, Julien JP, de Taeye SW, Garces F, Guttman M, Ozorowski G, Pritchard LK, Behrens AJ, Go EP, Burger JA, Schermer EE, Sliepen K, Ketas TJ, Pugach P, Yasmeen A, Cottrell CA, Torres JL, Vavourakis CD, van Gils MJ, LaBranche C, Montefiori DC, Desaire H, Crispin M, Klasse PJ, Lee KK, Moore JP, Ward AB, Wilson IA, Sanders RW. 

Cell Rep. 2017 Aug 22;20(8):1805-1817. doi: 10.1016/j.celrep.2017.07.077.

 

Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7.

Plotnik D, Guo W, Cleveland B, von Haller P, Eng JK, Guttman M, Lee KK, Arthos J, Hu SL. 

J Virol. 2017 Oct 13;91(21):e01005-17. doi: 10.1128/JVI.01005-17.

 

Computational Design of Trimeric Influenza-neutralizing Proteins Targeting the Hemagglutinin Receptor Binding Site.

Strauch EM, Bernard SM, La D, Bohn AJ, Lee PS, Anderson CE, Nieusma T, Holstein CA, Garcia NK, Hooper KA, Ravichandran R, Nelson JW, Sheffler W, Bloom JD, Lee KK, Ward AB, Yager P, Fuller DH, Wilson IA, Baker D. 

Nature Biotechnol. 2017 Jul;35(7):667-671. doi: 10.1038/nbt.3907. 

 

2016

 

Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C.

Klasse PJ, LaBranche CC, Ketas TJ, Ozorowski G, Cupo A, Pugach P, Ringe RP, Golabek M, van Gils MJ, Guttman M, Lee KK, Wilson IA, Butera ST, Ward AB, Montefiori DC, Sanders RW, Moore JP. 

PLoS Pathog. 2016 Sep 14;12(9):e1005864. doi: 10.1371/journal.ppat.1005864. 

 

Epitope-Independent Purification of Native-Like Envelope Trimers from Diverse HIV-1 Isolates.

Verkerke HP, Williams JA, Guttman M, Simonich CA, Liang Y, Filipavicius M, Hu SL, Overbaugh J, Lee KK. 

J Virol. 2016 Sep 29;90(20):9471-82. doi: 10.1128/JVI.01351-16. 

 

Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan.

Liang Y, Guttman M, Williams JA, Verkerke H, Alvarado D, Hu SL, Lee KK. 

J Virol. 2016 Sep 29;90(20):9224-36. doi: 10.1128/JVI.01116-16. 

 

Iterative Structure-based Improvement of a Fusion-glycoprotein Vaccine against RSV.

Joyce MG, Zhang B, Ou L, Chen M, Chuang GY, Druz A, Kong WP, Lai YT, Rundlet EJ, Tsybovsky Y, Yang Y, Georgiev IS, Guttman M, Lees CR, Pancera M, Sastry M, Soto C, Stewart-Jones GBE, Thomas PV, Van Galen JG, Baxa U, Lee KK, Mascola JR, Graham BS, Kwong PD. 

Nature Struct Mol Biol. 2016 Sep;23(9):811-820. doi: 10.1038/nsmb.3267. 

 

Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies.

Davenport TM, Gorman J, Joyce MG, Zhou T, Soto C, Guttman M, Moquin S, Yang Y, Zhang B, Doria-Rose NA, Hu SL, Mascola JR, Kwong PD, Lee KK. 

Structure. 2016 Aug 2;24(8):1346-1357. doi: 10.1016/j.str.2016.06.012. 

 

HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant.

Simonich CA, Williams KL, Verkerke HP, Williams JA, Nduati R, Lee KK, Overbaugh J. 

Cell. 2016 Jun 30;166(1):77-87. doi: 10.1016/j.cell.2016.05.055. 

Visualization and Sequencing of Membrane Remodeling Leading to Influenza Virus Fusion.

Gui L, Ebner JL, Mileant A, Williams JA, Lee KK. 

J Virol. 2016 Jul 11;90(15):6948-6962. doi: 10.1128/JVI.00240-16.

 

Site-Specific Mapping of Sialic Acid Linkage Isomers by Ion Mobility Spectrometry.

Guttman M, Lee KK. 

Analytical Chem. 2016 May 17;88(10):5212-7. doi: 10.1021/acs.analchem.6b00265. 

Probing the Impact of Local Structural Dynamics of Conformational Epitopes on Antibody Recognition.

Liang Y, Guttman M, Davenport TM, Hu SL, Lee KK. 

Biochemistry. 2016 Apr 19;55(15):2197-213. doi: 10.1021/acs.biochem.5b01354. 

 

Tuning a High Transmission Ion Guide to Prevent Gas-Phase Proton Exchange During H/D Exchange MS Analysis.

Guttman M, Wales TE, Whittington D, Engen JR, Brown JM, Lee KK. 

J Am Soc Mass Spectrom. 2016 Apr;27(4):662-8. doi: 10.1007/s13361-015-1330-8. 

 

Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities that Enable Vaccine Design.

Gorman J, Soto C, Yang MM, Davenport TM, Guttman M, Bailer RT, Chambers M, Chuang GY, DeKosky BJ, Doria-Rose NA, Druz A, Ernandes MJ, Georgiev IS, Jarosinski MC, Joyce MG, Lemmin TM, Leung S, Louder MK, McDaniel JR, Narpala S, Pancera M, Stuckey J, Wu X, Yang Y, Zhang B, Zhou T; NISC Comparative Sequencing Program, Mullikin JC, Baxa U, Georgiou G, McDermott AB, Bonsignori M, Haynes BF, Moore PL, Morris L, Lee KK, Shapiro L, Mascola JR, Kwong PD. 

Nature Struct Mol Biol. 2016 Jan;23(1):81-90. doi: 10.1038/nsmb.3144. 

 

2015

 

Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

de Taeye SW, Ozorowski G, Torrents de la Peña A, Guttman M, Julien JP, van den Kerkhof TL, Burger JA, Pritchard LK, Pugach P, Yasmeen A, Crampton J, Hu J, Bontjer I, Torres JL, Arendt H, DeStefano J, Koff WC, Schuitemaker H, Eggink D, Berkhout B, Dean H, LaBranche C, Crotty S, Crispin M, Montefiori DC, Klasse PJ, Lee KK, Moore JP, Wilson IA, Ward AB, Sanders RW. 

Cell. 2015 Dec 17;163(7):1702-15. doi: 10.1016/j.cell.2015.11.056.

 

Local and global structural drivers for the photoactivation of the orange carotenoid protein.

Gupta S, Guttman M, Leverenz RL, Zhumadilova K, Pawlowski EG, Petzold CJ, Lee KK, Ralston CY, Kerfeld CA. 

Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):E5567-74. doi: 10.1073/pnas.1512240112. 

 

Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers.

Ringe RP, Yasmeen A, Ozorowski G, Go EP, Pritchard LK, Guttman M, Ketas TA, Cottrell CA, Wilson IA, Sanders RW, Cupo A, Crispin M, Lee KK, Desaire H, Ward AB, Klasse PJ, Moore JP. 

J Virol. 2015 Dec;89(23):12189-210. doi: 10.1128/JVI.01768-15.

 

Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.

Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG, Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T, Louder MK, O'Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schön A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, Kwong PD. 

Nature Struct Mol Biol. 2015 Jul;22(7):522-31. doi: 10.1038/nsmb.3051. 

 

HIV-1 neutralizing antibodies induced by native-like envelope trimers.

Sanders RW, van Gils MJ, Derking R, Sok D, Ketas TJ, Burger JA, Ozorowski G, Cupo A, Simonich C, Goo L, Arendt H, Kim HJ, Lee JH, Pugach P, Williams M, Debnath G, Moldt B, van Breemen MJ, Isik G, Medina-Ramírez M, Back JW, Koff WC, Julien JP, Rakasz EG, Seaman MS, Guttman M, Lee KK, Klasse PJ, LaBranche C, Schief WR, Wilson IA, Overbaugh J, Burton DR, Ward AB, Montefiori DC, Dean H, Moore JP. 

Science. 2015 Jul 10;349(6244):aac4223. doi: 10.1126/science.aac4223. 

 

Comparative glycoprofiling of HIV gp120 immunogens by capillary electrophoresis and MALDI mass spectrometry.

Guttman M, Váradi C, Lee KK, Guttman A. 

Electrophoresis. 2015 Jun;36(11-12):1305-13. doi: 10.1002/elps.201500054. 

 

Dynamic changes during acid-induced activation of influenza hemagglutinin.

Garcia NK, Guttman M, Ebner JL, Lee KK. 

Structure. 2015 Apr 7;23(4):665-76. doi: 10.1016/j.str.2015.02.006. 

 

Electron tomography imaging of surface glycoproteins on human parainfluenza virus 3: association of receptor binding and fusion proteins before receptor engagement.

Gui L, Jurgens EM, Ebner JL, Porotto M, Moscona A, Lee KK. 

mBio. 2015 Feb 17;6(1):e02393-14. doi: 10.1128/mBio.02393-14.

 

Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.

Guttman M, Cupo A, Julien JP, Sanders RW, Wilson IA, Moore JP, Lee KK. 

Nature Commun. 2015 Feb 5;6:6144. doi: 10.1038/ncomms7144.

 

2014

 

Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation.

Umbreit NT, Miller MP, Tien JF, Ortolá JC, Gui L, Lee KK, Biggins S, Asbury CL, Davis TN. 

Nature Commun. 2014 Sep 19;5:4951. doi: 10.1038/ncomms5951.

 

Control of RecBCD enzyme activity by DNA binding- and Chi hotspot-dependent conformational changes.

Taylor AF, Amundsen SK, Guttman M, Lee KK, Luo J, Ranish J, Smith GR. 

J Mol Biol. 2014 Oct 23;426(21):3479-99. doi: 10.1016/j.jmb.2014.07.017. 

 

CD4-induced activation in a soluble HIV-1 Env trimer.

Guttman M, Garcia NK, Cupo A, Matsui T, Julien JP, Sanders RW, Wilson IA, Moore JP, Lee KK. 

Structure. 2014 Jul 8;22(7):974-84. doi: 10.1016/j.str.2014.05.001. 

 

2013

 

Analysis of overlapped and noisy hydrogen/deuterium exchange mass spectra.

Guttman M, Weis DD, Engen JR, Lee KK. 

J Am Soc Mass Spectrom. 2013 Dec;24(12):1906-12. doi: 10.1007/s13361-013-0727-5. 

 

A functional interaction between gp41 and gp120 is observed for monomeric but not oligomeric, uncleaved HIV-1 Env gp140.

Guttman M, Lee KK. 

J Virol. 2013 Nov;87(21):11462-75. doi: 10.1128/JVI.01681-13. 

 

Hexamers of the type II secretion ATPase GspE from Vibrio cholerae with increased ATPase activity.

Lu C, Turley S, Marionni ST, Park YJ, Lee KK, Patrick M, Shah R, Sandkvist M, Bush MF, Hol WG.  

Structure. 2013 Sep 3;21(9):1707-17. doi: 10.1016/j.str.2013.06.027. 

 

Isolate-specific differences in the conformational dynamics and antigenicity of HIV-1 gp120.

Davenport TM, Guttman M, Guo W, Cleveland B, Kahn M, Hu SL, Lee KK. 

J Virol. 2013 Oct;87(19):10855-73. doi: 10.1128/JVI.01535-13. 

 

Purification of recombinant vaccinia virus-expressed monomeric HIV-1 gp120 to apparent homogeneity.

Guo W, Cleveland B, Davenport TM, Lee KK, Hu SL. 

Protein Expr Purif. 2013 Jul;90(1):34-9. doi: 10.1016/j.pep.2013.04.009. 

 

All-atom ensemble modeling to analyze small-angle x-ray scattering of glycosylated proteins.

Guttman M, Weinkam P, Sali A, Lee KK. 

Structure. 2013 Mar 5;21(3):321-31. doi: 10.1016/j.str.2013.02.004.

 

2012

 

Regulation of paramyxovirus fusion activation: the hemagglutinin-neuraminidase protein stabilizes the fusion protein in a pretriggered state.

Porotto M, Salah ZW, Gui L, DeVito I, Jurgens EM, Lu H, Yokoyama CC, Palermo LM, Lee KK, Moscona A. 

J Virol. 2012 Dec;86(23):12838-48. doi: 10.1128/JVI.01965-12. 

 

Solution structure, conformational dynamics, and CD4-induced activation in full-length, glycosylated, monomeric HIV gp120.

Guttman M, Kahn M, Garcia NK, Hu SL, Lee KK. 

J Virol. 2012 Aug;86(16):8750-64. doi: 10.1128/JVI.07224-11.

 

2011

 

Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide, a new antiviral strategy for influenza virus.

Lee KK, Pessi A, Gui L, Santoprete A, Talekar A, Moscona A, Porotto M. 

J Biol Chem. 2011 Dec 9;286(49):42141-42149. doi: 10.1074/jbc.M111.254243. 

 

The Prohead-I structure of bacteriophage HK97: implications for scaffold-mediated control of particle assembly and maturation.

Huang RK, Khayat R, Lee KK, Gertsman I, Duda RL, Hendrix RW, Johnson JE. 

J Mol Biol. 2011 May 6;408(3):541-54. doi: 10.1016/j.jmb.2011.01.016. 

 

2010

 

Architecture of a nascent viral fusion pore.

Lee KK. 

EMBO Journal. 2010 Apr 7;29(7):1299-311. doi: 10.1038/emboj.2010.13. 

 

INVITED REVIEW ARTICLES                                                           

 

New Biophysical Approaches Reveal the Dynamics and Mechanics of Type I Viral Fusion Machinery and Their Interplay with Membranes.

Benhaim MA, Lee KK. 

Viruses. 2020 Apr 8;12(4):413. doi: 10.3390/v12040413.

 

Bridging protein structure, dynamics, and function using hydrogen/deuterium-exchange mass spectrometry.

Hodge EA, Benhaim MA, Lee KK. 

Protein Sci. 2020 Apr;29(4):843-855. doi: 10.1002/pro.3790.

 

Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry.

Benhaim M, Lee KK, Guttman M. 

Protein Pept Lett. 2019;26(1):16-26. doi: 10.2174/0929866526666181212165037.

 

Single-Molecule Analysis of a Viral Fusion Protein Illuminates a Fusion-Active Intermediate State.

Benhaim M, Lee KK. 

Cell. 2018 Aug 9;174(4):775-777. doi: 10.1016/j.cell.2018.07.026.

 

Probing Structural Variation and Dynamics in the HIV-1 Env Fusion Glycoprotein.

Munro JB, Lee KK. 

Curr HIV Res. 2018;16(1):5-12. doi:10.2174/1570162X16666171222110025.

 

Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy.

Lee KK, Gui L.

PLoS Pathog. 2016 Jun 30;12(6):e1005625. doi: 10.1371/journal.ppat.1005625.

 

Dynamic Viral Glycoprotein Machines: Approaches for Probing Transient States That Drive Membrane Fusion.

Garcia NK, Lee KK. 

Viruses. 2016 Jan 11;8(1):15. doi: 10.3390/v8010015.

 

Isotope Labeling of Biomolecules: Structural Analysis of Viruses by HDX-MS.

Guttman M, Lee KK. 

Methods Enzymol. 2016;566:405-26. doi: 10.1016/bs.mie.2015.05.021. 

PRE-UNIVERSITY OF WASHINGTON

 

An unexpected twist in viral capsid maturation.

Gertsman I, Gan L, Guttman M, Lee K, Speir JA, Duda RL, Hendrix RW, Komives EA, Johnson JE. 

Nature. 2009 Apr 2;458(7238):646-50. doi: 10.1038/nature07686. 

 

Dynamics and stability in maturation of a T=4 virus.

Tang J, Lee KK, Bothner B, Baker TS, Yeager M, Johnson JE. 

J Mol Biol. 2009 Sep 25;392(3):803-12. doi: 10.1016/j.jmb.2009.07.038.

 

Virus capsid expansion driven by the capture of mobile surface loops.

Lee KK, Gan L, Tsuruta H, Moyer C, Conway JF, Duda RL, Hendrix RW, Steven AC, Johnson JE. 

Structure. 2008 Oct 8;16(10):1491-502. doi: 10.1016/j.str.2008.06.014.

 

Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation interpreted by electron cryo-microscopy and X-ray crystallography.

Wikoff WR, Conway JF, Tang J, Lee KK, Gan L, Cheng N, Duda RL, Hendrix RW, Steven AC, Johnson JE. 

J Struct Biol. 2006 Mar;153(3):300-6. doi: 10.1016/j.jsb.2005.11.009. 

 

Cooperative reorganization of a 420 subunit virus capsid.

Lee KK, Tsuruta H, Hendrix RW, Duda RL, Johnson JE. 

J Mol Biol. 2005 Sep 23;352(3):723-35. doi: 10.1016/j.jmb.2005.07.024.

 

Maturation of a tetravirus capsid alters the dynamic properties and creates a metastable complex.

Bothner B, Taylor D, Jun B, Lee KK, Siuzdak G, Schultz CP, Johnson JE. 

Virology. 2005 Mar 30;334(1):17-27. doi: 10.1016/j.virol.2005.01.017.

 

Evidence that a local refolding event triggers maturation of HK97 bacteriophage capsid.

Lee KK, Gan L, Tsuruta H, Hendrix RW, Duda RL, Johnson JE. 

J Mol Biol. 2004 Jul 9;340(3):419-33. doi: 10.1016/j.jmb.2004.05.008.

 

Small compounds targeted to subunit interfaces arrest maturation in a nonenveloped, icosahedral animal virus.

Lee KK, Tang J, Taylor D, Bothner B, Johnson JE. 

J Virol. 2004 Jul;78(13):7208-16. doi: 10.1128/JVI.78.13.7208-7216.2004.

Complementary approaches to structure determination of icosahedral viruses.

Lee KK, Johnson JE. 

Curr Opin Struct Biol. 2003 Oct;13(5):558-69. doi: 10.1016/j.sbi.2003.09.007.

 

Experimental pK(a) values of buried residues: analysis with continuum methods and role of water penetration.

Fitch CA, Karp DA, Lee KK, Stites WE, Lattman EE, García-Moreno E B. 

Biophys J. 2002 Jun;82(6):3289-304. doi: 10.1016/s0006-3495(02)75670-1.

 

Electrostatic effects in highly charged proteins: salt sensitivity of pKa values of histidines in staphylococcal nuclease.

Lee KK, Fitch CA, Lecomte JT, García-Moreno E B. 

Biochemistry. 2002 Apr 30;41(17):5656-67. doi: 10.1021/bi0119417.

 

Distance dependence and salt sensitivity of pairwise, coulombic interactions in a protein.

Lee KK, Fitch CA, García-Moreno E B. 

Protein Sci. 2002 May;11(5):1004-16. doi: 10.1110/ps.4700102.