PDBsum entry 2ljd

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Membrane protein, cell adhesion PDB id
Protein chain
47 a.a.
PDB id:
Name: Membrane protein, cell adhesion
Title: Monophosphorylated (747py) beta3 integrin cytoplasmic tail u membrane mimetic conditions
Structure: Integrin beta-3. Chain: a. Fragment: cytoplasmic domain residues 742-788. Synonym: platelet membrane glycoprotein iiia, gpiiia. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: itgb3, gp3a. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 15 models
Authors: L.Deshmukh,O.Vinogradova
Key ref: L.Deshmukh et al. (2011). Tyrosine phosphorylation as a conformational switch: a case study of integrin β3 cytoplasmic tail. J Biol Chem, 286, 40943-40953. PubMed id: 21956114
11-Sep-11     Release date:   05-Oct-11    
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Protein chain
Pfam   ArchSchema ?
P05106  (ITB3_HUMAN) -  Integrin beta-3
788 a.a.
47 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integrin complex   1 term 
  Biological process     cell adhesion   7 terms 
  Biochemical function     receptor activity     1 term  


J Biol Chem 286:40943-40953 (2011)
PubMed id: 21956114  
Tyrosine phosphorylation as a conformational switch: a case study of integrin β3 cytoplasmic tail.
L.Deshmukh, N.Meller, N.Alder, T.Byzova, O.Vinogradova.
Reversible protein phosphorylation is vital for many fundamental cellular processes. The actual impact of adding and removing phosphate group(s) is 3-fold: changes in the local/global geometry, alterations in the electrostatic potential and, as the result of both, modified protein-target interactions. Here we present a comprehensive structural investigation of the effects of phosphorylation on the conformational as well as functional states of a crucial cell surface receptor, α(IIb)β(3) integrin. We have analyzed phosphorylated (Tyr(747) and Tyr(759)) β(3) integrin cytoplasmic tail (CT) primarily by NMR, and our data demonstrate that under both aqueous and membrane-mimetic conditions, phosphorylation causes substantial conformational rearrangements. These changes originate from novel ionic interactions and revised phospholipid binding. Under aqueous conditions, the critical Tyr(747) phosphorylation prevents β(3)CT from binding to its heterodimer partner α(IIb)CT, thus likely maintaining an activated state of the receptor. This conclusion was tested in vivo and confirmed by integrin-dependent endothelial cells adhesion assay. Under membrane-mimetic conditions, phosphorylation results in a modified membrane embedding characterized by significant changes in the secondary structure pattern and the overall fold of β(3)CT. Collectively these data provide unique molecular insights into multiple regulatory roles of phosphorylation.