1K34

Crystal structure analysis of gp41 core mutant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Interhelical interactions in the gp41 core: implications for activation of HIV-1 membrane fusion.

Wang, S.York, J.Shu, W.Stoller, M.O.Nunberg, J.H.Lu, M.

(2002) Biochemistry 41: 7283-7292

  • DOI: https://doi.org/10.1021/bi025648y
  • Primary Citation of Related Structures:  
    1K33, 1K34

  • PubMed Abstract: 

    The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein complex (gp120-gp41) promotes viral entry by mediating the fusion of viral and cellular membranes. Formation of a stable trimer-of-hairpins structure in the gp41 ectodomain brings the two membranes into proximity, leading to membrane fusion. The core of this hairpin structure is a six-helix bundle in which three carboxyl-terminal outer helices pack against an inner trimeric coiled coil. Here we investigate the role of these conserved interhelical interactions on the structure and function of both the envelope glycoprotein and the gp41 core. We have replaced each of the eight amino acids at the buried face of the carboxyl-terminal helix with a representative amino acid, alanine. Structural and physicochemical characterization of the alanine mutants shows that hydrophobic interactions are a dominant factor in the stabilization of the six-helix bundle. Alanine substitutions at the Trp628, Trp631, Ile635, and Ile642 residues also affected envelope processing and/or gp120-gp41 association and abrogated the ability of the envelope glycoprotein to mediate cell-cell fusion. These results suggest that the amino-terminal region of the gp41 outer-layer alpha-helix plays a key role in the sequence of events associated with HIV-1 entry and have implications for the development of antibodies and small-molecule inhibitors of this conserved element.


  • Organizational Affiliation

    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transmembrane glycoprotein GP4168Human immunodeficiency virus 1Mutation(s): 1 
UniProt
Find proteins for P04578 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04578 
Go to UniProtKB:  P04578
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04578
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.88 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.197 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.214α = 90
b = 52.214β = 90
c = 60.904γ = 120
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2001-10-10 
  • Deposition Author(s): Shu, W., Lu, M.

Revision History  (Full details and data files)

  • Version 1.0: 2001-10-10
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-08-09
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2021-10-27
    Changes: Database references, Refinement description
  • Version 1.5: 2024-02-07
    Changes: Data collection