Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition.
Amino Acid Sequence
Antibodies, Neutralizing
/ immunology
Cell Line
Cryoelectron Microscopy
/ methods
HIV Antibodies
/ immunology
HIV Envelope Protein gp120
/ immunology
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunoglobulin Fab Fragments
/ metabolism
Protein Binding
Protein Multimerization
env Gene Products, Human Immunodeficiency Virus
/ immunology
HIV-1 envelope trimer
PCT64
PG9
PGDM1400
PGT145
V1V2 apex recognition
broadly neutralizing antibody
multidonor antibody class
tyrosine sulfation
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
02
08
2019
revised:
07
01
2020
accepted:
16
03
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
28
4
2021
Statut:
ppublish
Résumé
Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 class. The mode of recognition, however, has been unclear for the most potent of the V1V2 apex-targeting antibodies, CAP256-VRC26.25 (named for donor-lineage.clone and referred to hereafter as VRC26.25). Here, we determine the cryoelectron microscopy structure at 3.7 Å resolution of the antigen-binding fragment of VRC26.25 in complex with the Env trimer thought to have initiated the lineage. The 36-residue protruding loop of VRC26.25 displays recognition incorporating both strand-C interactions similar to the PG9 class and V1V2 apex insertion similar to the PGT145 class. Structural elements of separate antibody classes can thus intermingle to form a "combined" class, which in this case yields an antibody of extraordinary potency.
Identifiants
pubmed: 32268107
pii: S2211-1247(20)30366-1
doi: 10.1016/j.celrep.2020.03.052
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
Immunoglobulin Fab Fragments
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107488Subventions
Organisme : NIAID NIH HHS
ID : U01 AI116086
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.