Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail
Dense surface glycosylation on the HIV-1 envelope (Env) protein acts as a shield from the adaptive immune system. However, the molecular complexity and flexibility of glycans make experimental studies a challenge. Here we have integrated high-throughput atomistic modeling of fully glycosylated HIV-1 Env with graph theory to capture immunologically important features of the shield topology. This is the first complete all-atom model of HIV-1 Env SOSIP glycan shield that includes both oligomannose and complex glycans, providing physiologically relevant insights of the glycan shield. This integrated approach including quantitative comparison with cryo-electron microscopy data provides hitherto unexplored details of the native shield architecture and its difference from the high-mannose glycoform. Here, we have also derived a measure to quantify the shielding effect over the antigenic protein surface that defines regions of relative vulnerability and resilience of the shield and can be harnessed for rational immunogen design.
- Research Organization:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)
- Grant/Contract Number:
- 89233218CNA000001; UM1 AI100645; UM1 AI144371; UM1 AI100663; UM1 AI144462; OPP1115782
- OSTI ID:
- 1730987
- Alternate ID(s):
- OSTI ID: 1727417
- Report Number(s):
- LA-UR-20-29404; S2589004220310336; 101836; PII: S2589004220310336
- Journal Information:
- iScience, Journal Name: iScience Vol. 23 Journal Issue: 12; ISSN 2589-0042
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- Netherlands
- Language:
- English
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