PDBsum entry 3f58

Immune system

PDB id: 3f58

Contents

Protein chains

215 a.a. *

228 a.a. *

11 a.a. *

Waters ×1

* Residue conservation analysis

PDB id:

3f58

Name:

Immune system

Title:

Igg1 fab fragment (58.2) complex with 12-residue cyclic peptide (including residues 315-324 of HIV-1 gp120 (mn isolate); h315s mutation

Structure:

Protein (immunoglobulin gamma i (58.2)). Chain: l. Fragment: light chain of fab. Synonym: fab 58.2. Protein (immunoglobulin gamma i (58.2)). Chain: h. Fragment: heavy chain of fab. Synonym: fab 58.2. Protein (cyclic peptide (gp120)).

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Synthetic: yes. Other_details: 12 residue hydrazone-linked cyclic peptide was chemically synthesized from residues 316-324 of HIV-1 gp120 strain mn.

Biol. unit:

Trimer (from PQS)

Resolution:

2.80Å R-factor: 0.200

Authors:

R.L.Stanfield,E.Cabezas,A.C.Satterthwait,E.A.Stura,A.T.Profy, I.A.Wilson

Key ref:

R.Stanfield et al. (1999). Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs. Structure, 7, 131-142. PubMed id: 10368281 DOI: 10.1016/S0969-2126(99)80020-3

Date:

23-Oct-98 Release date: 09-Feb-99

Protein chain

No UniProt id for this chain

Struc: 215 a.a.

Protein chain

No UniProt id for this chain

Struc: 228 a.a.

Protein chain

No UniProt id for this chain

Struc: 11 a.a.

DOI no: 10.1016/S0969-2126(99)80020-3

Structure 7:131-142 (1999)

PubMed id: 10368281

Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs.

R.Stanfield, E.Cabezas, A.Satterthwait, E.Stura, A.Profy, I.Wilson.

ABSTRACT

BACKGROUND: The third hypervariable (V3) loop of HIV-1 gp120 has been termed the principal neutralizing determinant (PND) of the virus and is involved in many aspects of virus infectivity. The V3 loop is required for viral entry into the cell via membrane fusion and is believed to interact with cell surface chemokine receptors on T cells and macrophages. Sequence changes in V3 can affect chemokine receptor usage, and can, therefore, modulate which types of cells are infected. Antibodies raised against peptides with V3 sequences can neutralize laboratory-adapted strains of the virus and inhibit syncytia formation. Fab fragments of these neutralizing antibodies in complex with V3 loop peptides have been studied by X-ray crystallography to determine the conformation of the V3 loop. RESULTS: We have determined three crystal structures of Fab 58.2, a broadly neutralizing antibody, in complex with one linear and two cyclic peptides the amino acid sequence of which comes from the MN isolate of the gp120 V3 loop. Although the peptide conformations are very similar for the linear and cyclic forms, they differ from that seen for the identical peptide bound to a different broadly neutralizing antibody, Fab 59.1, and for a similar peptide bound to the MN-specific Fab 50.1. The conformational difference in the peptide is localized around residues Gly-Pro-Gly-Arg, which are highly conserved in different HIV-1 isolates and are predicted to adopt a type II beta turn. CONCLUSIONS: The V3 loop can adopt at least two different conformations for the highly conserved Gly-Pro-Gly-Arg sequence at the tip of the loop. Thus, the HIV-1 V3 loop has some inherent conformational flexibility that may relate to its biological function.

Selected figure(s)

Figure 2.
Figure 2. Stereoviews of the X-ray structures of the Fab 58.2–peptide complexes. (a) The Fab 58.2–Aib142 complex. The Cα trace is shown for the light chain (cyan) and heavy chain (blue) of the Fab. All atoms of the bound peptide are shown in red. Every tenth Cα atom is highlighted with a sphere and some atoms are labeled. (b) The Fab 58.2–His loop complex. (c) The Fab 58.2–Ser loop complex. Figures were made with the program MOLSCRIPT [74] .

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 131-142) copyright 1999.

Figure was selected by an automated process.