3JWD

Structure of HIV-1 gp120 with gp41-Interactive Region: Layered Architecture and Basis of Conformational Mobility


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.201 

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This is version 1.3 of the entry. See complete history


Literature

Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

Pancera, M.Majeed, S.Ban, Y.E.Chen, L.Huang, C.C.Kong, L.Kwon, Y.D.Stuckey, J.Zhou, T.Robinson, J.E.Schief, W.R.Sodroski, J.Wyatt, R.Kwong, P.D.

(2010) Proc Natl Acad Sci U S A 107: 1166-1171

  • DOI: https://doi.org/10.1073/pnas.0911004107
  • Primary Citation of Related Structures:  
    3JWD, 3JWO

  • PubMed Abstract: 

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 GP120 ENVELOPE GLYCOPROTEINA,
E [auth B]
379Human immunodeficiency virus 1Mutation(s): 0 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
T-cell surface glycoprotein CD4B [auth C],
F [auth D]
184Homo sapiensMutation(s): 0 
Gene Names: CD4
UniProt & NIH Common Fund Data Resources
Find proteins for P01730 (Homo sapiens)
Explore P01730 
Go to UniProtKB:  P01730
PHAROS:  P01730
GTEx:  ENSG00000010610 
Entity Groups  
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UniProt GroupP01730
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
FAB 48D LIGHT CHAINC [auth L],
G [auth O]
213Homo sapiensMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
FAB 48D HEAVY CHAIND [auth H],
H [auth P]
220Homo sapiensMutation(s): 0 
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AA [auth B]
BA [auth B]
I [auth A]
J [auth A]
K [auth A]
AA [auth B],
BA [auth B],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth B],
T [auth B],
U [auth B],
V [auth B],
W [auth B],
X [auth B],
Y [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
CA [auth P],
Z [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
YCM
Query on YCM
C [auth L],
G [auth O]
L-PEPTIDE LINKINGC5 H10 N2 O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.201 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.112α = 90
b = 172.954β = 90
c = 193.144γ = 90
Software Package:
Software NamePurpose
AMoREphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Refinement description, Structure summary