PDBsum entry 4zmj

Viral protein

PDB id: 4zmj

Contents

Protein chains

450 a.a.

123 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-MAN

NAG-NAG ×2

NAG ×15

PDB id:

4zmj

Name:

Viral protein

Title:

Crystal structure of ligand-free bg505 sosip.664 HIV-1 env trimer

Structure:

Envelope glycoprotein gp160. Chain: g. Engineered: yes. Mutation: yes. Envelope glycoprotein gp160. Chain: b. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Gene: env. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell: hek293 gnti-/-.

Resolution:

3.31Å R-factor: 0.268 R-free: 0.286

Authors:

Y.D.Kwon,P.D.Kwong

Key ref:

Y.D.Kwon et al. (2015). Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Biol, 22, 522-531. PubMed id: 26098315 DOI: 10.1038/nsmb.3051

Date:

04-May-15 Release date: 24-Jun-15

Protein chain

Q2N0S6  (Q2N0S6_HV1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1

Seq: 860 a.a.

Struc: 450 a.a.*

Protein chain

Q2N0S6  (Q2N0S6_HV1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1

Seq: 860 a.a.

Struc: 123 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/nsmb.3051

Nat Struct Biol 22:522-531 (2015)

PubMed id: 26098315

Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env.

Y.D.Kwon, M.Pancera, P.Acharya, I.S.Georgiev, E.T.Crooks, J.Gorman, M.G.Joyce, M.Guttman, X.Ma, S.Narpala, C.Soto, D.S.Terry, Y.Yang, T.Zhou, G.Ahlsen, R.T.Bailer, M.Chambers, G.Y.Chuang, N.A.Doria-Rose, A.Druz, M.A.Hallen, A.Harned, T.Kirys, M.K.Louder, S.O'Dell, G.Ofek, K.Osawa, M.Prabhakaran, M.Sastry, G.B.Stewart-Jones, J.Stuckey, P.V.Thomas, T.Tittley, C.Williams, B.Zhang, H.Zhao, Z.Zhou, B.R.Donald, L.K.Lee, S.Zolla-Pazner, U.Baxa, A.Schön, E.Freire, L.Shapiro, K.K.Lee, J.Arthos, J.B.Munro, S.C.Blanchard, W.Mothes, J.M.Binley, A.B.McDermott, J.R.Mascola, P.D.Kwong.

ABSTRACT

As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate: a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.