PDBsum entry: 2oqj

Immune system

PDB-id: 2oqj

Main view

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

211 a.a. *

224 a.a. *

18 a.a. *

20 a.a. *

17 a.a. *

19 a.a. *

* Residue conservation analysis

Tools

Clefts Calculation

Bottom view	Right view

PDB id:

2oqj

Name:

Immune system

Title:

Crystal structure analysis of fab 2g12 in complex with peptide 2g12.1

Structure:

Fab 2g12 light chain. Chain: a, d, g, j. Fab 2g12 heavy chain. Chain: b, e, h, k. Peptide 2g12.1 (acppshvldmrsgtclaaegk). Chain: c, f, i, l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: fab 2g12 light chain. Other_details: fab 2g12 heavy chain. Synthetic: yes. Other_details: synthetic peptide derived from a phage- displayed peptide library

UniProt:

Chain A: Q6PIH4 (Q6PIH4_HUMAN)

Chains B, E, H, K: Q6N089 (Q6N089_HUMAN)

Seq:

Struc:

Seq:

472 a.a.

Struc:

224 a.a.*

Key:	PfamA domain
Secondary structure	CATH domain

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

Resolution:

2.80Å

R-factor:

0.236

R-free:

0.275

Authors:

D.A.Calarese,R.L.Stanfield,A.Menendez,J.K.Scott,I.A.Wilson

Key ref:

A.Menendez et al. (2008). A peptide inhibitor of HIV-1 neutralizing antibody 2G12 is not a structural mimic of the natural carbohydrate epitope on gp120.. FASEB J, 22, 1380-1392. [PubMed id: 18198210] [DOI: 10.1096/fj.07-8983com]

Date:

31-Jan-07

Release date:

15-Jan-08

Related entries:

1op3
the same protein complexed with man1-2man
1op5
the same protein complexed with man9
1om3
the same protein, unliganded
1zls
the same protein complexed with man4
1zlu
the same protein complexed with man5
... plus others (see Header records)

Quick_links

Procheck

Key reference

DOI no: 10.1096/fj.07-8983com

FASEB J 22:1380-1392 (2008)

PubMed id: 18198210

A peptide inhibitor of HIV-1 neutralizing antibody 2G12 is not a structural mimic of the natural carbohydrate epitope on gp120.

A.Menendez, D.A.Calarese, R.L.Stanfield, K.C.Chow, C.N.Scanlan, R.Kunert, H.Katinger, D.R.Burton, I.A.Wilson, J.K.Scott.

ABSTRACT

MAb 2G12 neutralizes HIV-1 by binding with high affinity to a cluster of high-mannose oligosaccharides on the envelope glycoprotein, gp120. Screening of phage-displayed peptide libraries with 2G12 identified peptides that bind specifically, with K(d)s ranging from 0.4 to 200 microM. The crystal structure of a 21-mer peptide ligand in complex with 2G12 Fab was determined at 2.8 A resolution. Comparison of this structure with previous structures of 2G12-carbohydrate complexes revealed striking differences in the mechanism of 2G12 binding to peptide vs. carbohydrate. The peptide occupies a site different from, but adjacent to, the primary carbohydrate-binding site on 2G12, and makes only slightly fewer contacts to the Fab than Man(9)GlcNAc(2) (51 vs. 56, respectively). However, only two antibody contacts with the peptide are hydrogen bonds in contrast to six with Man(9)GlcNAc(2), and only three of the antibody residues that interact with Man(9)GlcNAc(2) also contact the peptide. Thus, this mechanism of peptide binding to 2G12 does not support structural mimicry of the native carbohydrate epitope on gp120, since it neither replicates the oligosaccharide footprint on the antibody nor most of the contact residues. Moreover, 2G12.1 peptide is not an immunogenic mimic of the 2G12 epitope, since antisera produced against it did not bind gp120.