6X9V

HIV-1 Envelope Glycoprotein BG505 SOSIP.664, expressed in HEK293S cells and deglycosylated by endoglycosidase H, in complex with RM20A3 Fab

Summary for 6X9V

• Entry DOI: 10.2210/pdb6x9v/pdb
• EMDB information: 22108 22109 22110 22111 22112
• Descriptor: HIV-1 Envelope Glycoprotein BG505 SOSIP.664 gp120, HIV-1 Envelope Glycoprotein BG505 SOSIP.664 gp41, RM20A3 Fab Heavy Chain, ... (7 entities in total)
• Functional Keywords: hiv-1, envelope, glycoprotein, spike, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 4
• Total formula weight: 108319.19

Authors

Berndsen, Z.T.,Ward, A.B. (deposition date: 2020-06-03, release date: 2020-11-04, Last modification date: 2024-10-16)

Primary citation

Berndsen, Z.T.,Chakraborty, S.,Wang, X.,Cottrell, C.A.,Torres, J.L.,Diedrich, J.K.,Lopez, C.A.,Yates 3rd, J.R.,van Gils, M.J.,Paulson, J.C.,Gnanakaran, S.,Ward, A.B.
Visualization of the HIV-1 Env glycan shield across scales.
Proc.Natl.Acad.Sci.USA, 117:28014-28025, 2020

PubMed Abstract: The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis. Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels. We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield. This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env. Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility. Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production. Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.

PubMed: 33093196
DOI: 10.1073/pnas.2000260117

Experimental method

ELECTRON MICROSCOPY (3.5 Å)