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TitleStructural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.
Journal, issue, pagesStructure, Vol. 30, Issue 6, Page 862-875.e4, Year 2022
Publish dateJun 2, 2022
AuthorsTongqing Zhou / Lei Chen / Jason Gorman / Shuishu Wang / Young D Kwon / Bob C Lin / Mark K Louder / Reda Rawi / Erik-Stephane D Stancofski / Yongping Yang / Baoshan Zhang / Anna Forsman Quigley / Laura E McCoy / Lucy Rutten / Theo Verrips / Robin A Weiss / / Nicole A Doria-Rose / Lawrence Shapiro / Peter D Kwong /
PubMed AbstractNanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies ...Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.
External linksStructure / PubMed:35413243 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.76 - 3.61 Å
Structure data

23480

7lpn

EMDB-23480, PDB-7lpn:
Cryo-EM structure of llama J3 VHH antibody in complex with HIV-1 Env BG505 DS-SOSIP.664
Method: EM (single particle) / Resolution: 3.61 Å

PDB-7r73:
Crystal structure of llama VHH antibody D7 in complex with HIV-1 gp120 core
Method: X-RAY DIFFRACTION / Resolution: 1.76 Å

PDB-7r74:
Crystal structure of llama VHH antibody in complex with HIV-1 HXBC2 gp120 core
Method: X-RAY DIFFRACTION / Resolution: 2.76 Å

PDB-7ri1:
Crystal structure of anti-HIV llama VHH antibody J3 in complex with HIV-1 C1086 gp120
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

PDB-7ri2:
Crystal structure of anti-HIV llama VHH antibody A12 in complex with HIV-1 C1086 gp120
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

ChemComp-SO4:
SULFATE ION / Sulfate

Source
  • human immunodeficiency virus 1
  • lama glama (llama)
KeywordsVIRAL PROTEIN / CD4 / HIV-1 / SOSIP / Vaccine / IMMUNE SYSTEM / llama / antibody / VHH / gp120

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