2LYA

Structure of HIV-1 myr(-) matrix protein in complex with 1,2-dioctanoyl-sn-phosphatidylcholine


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Trio engagement via plasma membrane phospholipids and the myristoyl moiety governs HIV-1 matrix binding to bilayers.

Vlach, J.Saad, J.S.

(2013) Proc Natl Acad Sci U S A 110: 3525-3530

  • DOI: https://doi.org/10.1073/pnas.1216655110
  • Primary Citation of Related Structures:  
    2LYA, 2LYB

  • PubMed Abstract: 

    Localization of the HIV type-1 (HIV-1) Gag protein on the plasma membrane (PM) for virus assembly is mediated by specific interactions between the N-terminal myristoylated matrix (MA) domain and phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)]. The PM bilayer is highly asymmetric, and this asymmetry is considered crucial in cell function. In a typical mammalian cell, the inner leaflet of the PM is enriched in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and contains minor populations of phosphatidylcholine (PC) and PI(4,5)P(2). There is strong evidence that efficient binding of HIV-1 Gag to membranes is sensitive not only to lipid composition and net negative charge, but also to the hydrophobic character of the acyl chains. Here, we show that PS, PE, and PC interact directly with MA via a region that is distinct from the PI(4,5)P(2) binding site. Our NMR data also show that the myristoyl group is readily exposed when MA is bound to micelles or bicelles. Strikingly, our structural data reveal a unique binding mode by which the 2'-acyl chain of PS, PE, and PC lipids is buried in a hydrophobic pocket whereas the 1'-acyl chain is exposed. Sphingomyelin, a major lipid localized exclusively on the outer layer of the PM, does not bind to MA. Our findings led us to propose a trio engagement model by which HIV-1 Gag is anchored to the PM via the 1'-acyl chains of PI(4,5)P(2) and PS/PE/PC and the myristoyl group, which collectively bracket a basic patch projecting toward the polar leaflet of the membrane.


  • Organizational Affiliation

    Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Matrix protein p17137Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)Mutation(s): 0 
Gene Names: gag-pol
UniProt
Find proteins for P12497 (Human immunodeficiency virus type 1 group M subtype B (isolate NY5))
Explore P12497 
Go to UniProtKB:  P12497
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12497
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PC8
Query on PC8

Download Ideal Coordinates CCD File 
B [auth A]1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
C24 H49 N O8 P
YHIXRNNWDBPKPW-JOCHJYFZSA-O
Binding Affinity Annotations 
IDSourceBinding Affinity
PC8 PDBBind:  2LYA Kd: 6.50e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-13
    Type: Initial release
  • Version 1.1: 2013-03-06
    Changes: Database references
  • Version 1.2: 2013-04-03
    Changes: Database references