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TitleDevelopment of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2.
Journal, issue, pagesAdv Sci (Weinh), Vol. 9, Issue 15, Page e2200063, Year 2022
Publish dateMar 23, 2022
AuthorsNan Gao / Yanxin Gai / Lina Meng / Chu Wang / Wei Wang / Xiaojun Li / Tiejun Gu / Mark K Louder / Nicole A Doria-Rose / Kevin Wiehe / Alexandra F Nazzari / Adam S Olia / Jason Gorman / Reda Rawi / Wenmin Wu / Clayton Smith / Htet Khant / Natalia de Val / Bin Yu / Junhong Luo / Haitao Niu / Yaroslav Tsybovsky / Huaxin Liao / Thomas B Kepler / Peter D Kwong / John R Mascola / Chuan Qin / Tongqing Zhou / Xianghui Yu / Feng Gao /
PubMed AbstractUnderstanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 can be highly informative for HIV-1 vaccine development. A lineage of J038 bnAbs is now obtained from a long- ...Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 can be highly informative for HIV-1 vaccine development. A lineage of J038 bnAbs is now obtained from a long-term SHIV-infected macaque. J038 neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique "up" conformation for one of the V2 loops in the trimeric envelope glycoprotein and is heavily dependent on glycan, which provides nearly half of the binding surface. Their unmutated common ancestor neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for elicitation and maturation of V2-targeting bnAbs.
External linksAdv Sci (Weinh) / PubMed:35319830 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 4.2 Å
Structure data

24071

7mxd

EMDB-24071, PDB-7mxd:
Cryo-EM structure of broadly neutralizing V2-apex-targeting antibody J038 in complex with HIV-1 Env
Method: EM (single particle) / Resolution: 3.4 Å

24128

7n28

EMDB-24128, PDB-7n28:
Cryo-EM structure of broadly neutralizing V2-apex-targeting antibody J033 in complex with HIV-1 Env
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-PO4:
PHOSPHATE ION

ChemComp-MAN:
alpha-D-mannopyranose

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsIMMUNE SYSTEM/VIRAL PROTEIN / HIV-1 / SIV-1 / V2-apex / envelope glycoprotein / neutralizing antibody / glycan-dependent / IMMUNE SYSTEM-VIRAL PROTEIN complex

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