PDBsum entry 4jm2

Immune system/viral protein

PDB id: 4jm2

Contents

Protein chains

227 a.a.

214 a.a.

214 a.a.

220 a.a.

315 a.a.

175 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-MAN-MAN-MAN

NAG-NAG-BMA-MAN-MAN-MAN-MAN-MAN-MAN-MAN

NAG-NAG-BMA

PG4

NAG ×6

Waters ×1

PDB id:

4jm2

Name:

Immune system/viral protein

Title:

Crystal structure of pgt 135 fab in complex with gp120 core protein from HIV-1 strain jr-fl bound to cd4 and 17b fab

Structure:

Pgt 135 heavy chain. Chain: a. Fragment: fab. Engineered: yes. Pgt 135 light chain. Chain: b. Fragment: fab. Engineered: yes. 17b light chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Human immunodeficiency virus 1. HIV-1. Organism_taxid: 11676. Strain: jrfl.

Resolution:

3.10Å R-factor: 0.241 R-free: 0.285

Authors:

L.Kong,I.A.Wilson

Key ref:

L.Kong et al. (2013). Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Biol, 20, 796-803. PubMed id: 23708606 DOI: 10.1038/nsmb.2594

Date:

13-Mar-13 Release date: 29-May-13

Protein chain

No UniProt id for this chain

Struc: 227 a.a.

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 220 a.a.

Protein chain

Q75760  (Q75760_HV1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1

Seq: 847 a.a.

Struc: 315 a.a.*

Protein chain

P01730  (CD4_HUMAN) -  T-cell surface glycoprotein CD4 from Homo sapiens

Seq: 458 a.a.

Struc: 175 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nsmb.2594

Nat Struct Biol 20:796-803 (2013)

PubMed id: 23708606

Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120.

L.Kong, J.H.Lee, K.J.Doores, C.D.Murin, J.P.Julien, R.McBride, Y.Liu, A.Marozsan, A.Cupo, P.J.Klasse, S.Hoffenberg, M.Caulfield, C.R.King, Y.Hua, K.M.Le, R.Khayat, M.C.Deller, T.Clayton, H.Tien, T.Feizi, R.W.Sanders, J.C.Paulson, J.P.Moore, R.L.Stanfield, D.R.Burton, A.B.Ward, I.A.Wilson.

ABSTRACT

A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-Å crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization.