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PDBsum entry 1rn0

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protein Protein-protein interface(s) links
Cell adhesion PDB id
1rn0
Jmol
Contents
Protein chains
451 a.a.
244 a.a.
Theoretical model
PDB id:
1rn0
Name: Cell adhesion
Title: A refined three-dimensional model of integrin aiibb3
Structure: Integrin alpha-iib. Chain: a. Fragment: swissprot residues 32-482. Synonym: platelet membrane glycoprotein iib, gpalpha iib, gpiib, cd41 antigen. Integrin beta-3. Chain: b. Fragment: swissprot residues 135-378. Synonym: platelet membrane glycoprotein iiia, gpiiia, cd61
Source: Homo sapiens. Human. Human
Authors: M.Filizola,S.A.Hassan,A.Artoni,B.S.Coller,H.Weinstein
Key ref:
M.Filizola et al. (2004). Mechanistic insights from a refined three-dimensional model of integrin alphaIIbbeta3. J Biol Chem, 279, 24624-24630. PubMed id: 15056669 DOI: 10.1074/jbc.M400243200
Date:
28-Nov-03     Release date:   04-May-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08514  (ITA2B_HUMAN) -  Integrin alpha-IIb
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1039 a.a.
451 a.a.*
Protein chain
Pfam   ArchSchema ?
P05106  (ITB3_HUMAN) -  Integrin beta-3
Seq:
Struc:
 
Seq:
Struc:
788 a.a.
244 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1074/jbc.M400243200 J Biol Chem 279:24624-24630 (2004)
PubMed id: 15056669  
 
 
Mechanistic insights from a refined three-dimensional model of integrin alphaIIbbeta3.
M.Filizola, S.A.Hassan, A.Artoni, B.S.Coller, H.Weinstein.
 
  ABSTRACT  
 
The integrin alpha(IIb)beta(3) plays an important role in platelet function, and abnormalities of this protein result in a serious bleeding disorder, known as Glanzmann thrombasthenia. Although crystallographic data exist for the related integrin alpha(V)beta(3), to date, there are no high resolution structures of integrin alpha(IIb)beta(3) available in the literature. Therefore, it is still unclear how specific elements of the alpha(IIb) subunit contribute to integrin alpha(IIb)beta(3) function. Here we describe a refined model of the alpha(IIb) N-terminal portion of integrin alpha(IIb)beta(3) obtained by using the alpha(V)beta(3) template combined with a new method for predicting the conformations of the unique alpha(IIb) loop regions comprising residues 71-85, 114-125, and 148-164. The refined model was probed based on a structural prediction that differentiates it from standard homology models: specifically, that Lys-118 of alpha(IIb) contacts Glu-171 of beta(3). To test this hypothesis experimentally, the mutant integrin chains alpha(IIb) K118C and beta(3) E171C were cotransfected into HEK 293 cells. We show that the cells expressed the mutants alpha(IIb)beta(3) on their surface as a disulfide-linked dimer, supporting the close proximity between alpha(IIb) Lys-118 and beta(3) Glu-171 predicted from the refined model. This validated model provides a specific structural context for the analysis and interpretation of structure-function relations of integrin alpha(IIb)beta(3). In addition, it suggests mechanistic hypotheses pertaining to both naturally occurring mutations responsible for Glanzmann thrombasthenia and to point mutations that affect ligand binding.
 
  Selected figure(s)  
 
Figure 2.
FIG. 2. Superposition of the [V] [3] crystal structure (magenta) in complex with RGD (colored by atom code) with our proposed model of the [IIb]-(1-451)- [3] (109-352) complex (green for [IIb]and red for [3]). The three refined interacting loops of the [IIb] subunit are shown in brown (loop 71-85), orange (114-125), and blue (148-164).
Figure 5.
FIG. 5. Residues that affect ligand binding (magenta and orange) in the context of our refined [IIb]-(1-451) model (in green) and the [3] subunit (in red). In particular, residues in orange belong to the loops refined here.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 24624-24630) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18195363 M.F.Penet, M.Abou-Hamdan, N.Coltel, E.Cornille, G.E.Grau, M.de Reggi, and B.Gharib (2008).
Protection against cerebral malaria by the low-molecular-weight thiol pantethine.
  Proc Natl Acad Sci U S A, 105, 1321-1326.  
16729264 E.L.Mehler, S.A.Hassan, S.Kortagere, and H.Weinstein (2006).
Ab initio computational modeling of loops in G-protein-coupled receptors: lessons from the crystal structure of rhodopsin.
  Proteins, 64, 673-690.  
16594640 H.Weinstein (2005).
Hallucinogen actions on 5-HT receptors reveal distinct mechanisms of activation and signaling by G protein-coupled receptors.
  AAPS J, 7, E871-E884.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.