PDBsum entry 6vpy

Immune system

PDB id: 6vpy

Contents

Protein chains

208 a.a.

216 a.a.

Ligands

GOL ×2

Metals

_CL

Waters ×303

PDB id:

6vpy

Name:

Immune system

Title:

I33m (i3.2 mutant from ch103 lineage)

Structure:

I33m light chain. Chain: b, l. Fragment: fab,fab. Engineered: yes. I33m heavy chain. Chain: a, h. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hek293t. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Expression_system_taxid: 9606

Resolution:

2.36Å R-factor: 0.187 R-free: 0.223

Authors:

D.Fera,J.Zhou

Key ref:

J.O.Zhou et al. (2020). The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage. Front Immunol, 11, 1529. PubMed id: 32765530 DOI: 10.3389/fimmu.2020.01529

Date:

04-Feb-20 Release date: 15-Jul-20

Protein chains

Q8N355  (Q8N355_HUMAN) -  IGL@ protein from Homo sapiens

Seq: 234 a.a.

Struc: 208 a.a.*

Protein chains

Q6GMX6  (Q6GMX6_HUMAN) -  IGH@ protein from Homo sapiens

Seq: 465 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 56 residue positions (black crosses)

DOI no: 10.3389/fimmu.2020.01529

Front Immunol 11:1529 (2020)

PubMed id: 32765530

The Effects of Framework Mutations at the Variable Domain Interface on Antibody Affinity Maturation in an HIV-1 Broadly Neutralizing Antibody Lineage.

J.O.Zhou, H.A.Zaidi, T.Ton, D.Fera.

ABSTRACT

Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framework region are not well understood. Throughout affinity maturation, the CH103 broadly neutralizing antibody lineage, from an individual designated CH505, altered the orientation of one of its antibody variable domains. The change in orientation was a response to insertions in the variable loop 5 (V5) of the HIV envelope. In this study, we generated CH103 lineage antibody variants in which residues in the variable domain interface were mutated, and measured the binding to both autologous and heterologous HIV-1 envelopes. Our data show that very few mutations in an early intermediate antibody of the lineage can improve binding toward both autologous and heterologous HIV-1 envelopes. We also crystallized an antibody mutant to show that framework mutations alone can result in a shift in relative orientations of the variable domains. Taken together, our results demonstrate the functional importance of residues located outside the antigen-binding site in affinity maturation.