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PDBsum entry 2vdp
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protein ligands metals Protein-protein interface(s) links
Cell adhesion/immune system PDB id
2vdp

 

 

 

 

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Contents
Protein chains
452 a.a. *
455 a.a. *
219 a.a. *
214 a.a. *
Ligands
GLY-ALA-LYS-GLN-
ALA-GLY-ASP-VAL
NAG-NAG-MAN-MAN-
MAN
NAG-NAG-MAN-MAN-
MAN-MAN-MAN
GOL ×2
NAG ×3
Metals
_CA ×6
_MG
Waters ×557
* Residue conservation analysis
PDB id:
2vdp
Name: Cell adhesion/immune system
Title: Integrin alphaiibbeta3 headpiece bound to fibrinogen gamma chain peptide,lggakqagdv
Structure: Integrin alpha-iib. Chain: a. Fragment: headpiece, residues 32-483. Synonym: platelet membrane glycoprotein iib, gpalpha iib, gpiib, integrin alpha-iib heavy chain. Engineered: yes. Integrin beta-3. Chain: b. Fragment: headpiece, residues 27-487.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: lec 3.2.8.1. Synthetic: yes. Mus musculus. Mouse.
Resolution:
2.80Å     R-factor:   0.158     R-free:   0.204
Authors: T.A.Springer,J.Zhu,T.Xiao
Key ref: T.A.Springer et al. (2008). Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3. J Cell Biol, 182, 791-800. PubMed id: 18710925
Date:
10-Oct-07     Release date:   02-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08514  (ITA2B_HUMAN) -  Integrin alpha-IIb from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1039 a.a.
452 a.a.
Protein chain
Pfam   ArchSchema ?
P05106  (ITB3_HUMAN) -  Integrin beta-3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		788 a.a.
455 a.a.
Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Protein chain
No UniProt id for this chain
Struc: 214 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
J Cell Biol 182:791-800 (2008)
PubMed id: 18710925  
 
 
Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3.
T.A.Springer, J.Zhu, T.Xiao.
 
  ABSTRACT  
 
Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin alpha(IIb)beta(3) on platelets, resulting in platelet aggregation. alpha(v)beta(3) binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's alpha subunit. alpha(IIb)beta(3) also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the gamma subunit (gammaC peptide). These distinct modes of fibrinogen binding enable alpha(IIb)beta(3) and alpha(v)beta(3) to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin alpha(IIb)beta(3)-gammaC peptide interface, and, for comparison, integrin alpha(IIb)beta(3) bound to a lamprey gammaC primordial RGD motif. Compared with RGD, the GAKQAGDV motif in gammaC adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg(2+) ion binds the gammaC Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca(2+) ion binds the gammaC C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered gammaC peptide enhances our understanding of the involvement of gammaC peptide and integrin alpha(IIb)beta(3) in hemostasis and thrombosis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20804530 M.Landau, and N.Rosenberg (2011).
Molecular insight into human platelet antigens: structural and evolutionary conservation analyses offer new perspective to immunogenic disorders.
  Transfusion, 51, 558-569.  
20033057 C.Xie, J.Zhu, X.Chen, L.Mi, N.Nishida, and T.A.Springer (2010).
Structure of an integrin with an alphaI domain, complement receptor type 4.
  EMBO J, 29, 666-679.
PDB codes: 3k6s 3k71 3k72
20230529 D.Dotzauer, S.Wolfenstetter, D.Eibert, S.Schneider, P.Dietrich, and N.Sauer (2010).
Novel PSI domains in plant and animal H+-inositol symporters.
  Traffic, 11, 767-781.  
20679525 J.Zhu, J.Zhu, A.Negri, D.Provasi, M.Filizola, B.S.Coller, and T.A.Springer (2010).
Closed headpiece of integrin αIIbβ3 and its complex with an αIIbβ3-specific antagonist that does not induce opening.
  Blood, 116, 5050-5059.
PDB codes: 3nid 3nif 3nig
20152825 S.Fraichard, A.L.Bougé, T.Kendall, I.Chauvel, H.Bouhin, and T.A.Bunch (2010).
Tenectin is a novel alphaPS2betaPS integrin ligand required for wing morphogenesis and male genital looping in Drosophila.
  Dev Biol, 340, 504-517.  
20020534 V.Jallu, M.Dusseaux, S.Panzer, M.F.Torchet, N.Hezard, J.Goudemand, A.G.de Brevern, and C.Kaplan (2010).
AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function.
  Hum Mutat, 31, 237-246.  
21098296 Y.Pan, K.Zhang, J.Qi, J.Yue, T.A.Springer, and J.Chen (2010).
Cation-pi interaction regulates ligand-binding affinity and signaling of integrin alpha4beta7.
  Proc Natl Acad Sci U S A, 107, 21388-21393.  
19906580 A.E.Brown, and D.E.Discher (2009).
Conformational changes and signaling in cell and matrix physics.
  Curr Biol, 19, R781-R789.  
19561611 B.Bishop, A.R.Aricescu, K.Harlos, C.A.O'Callaghan, E.Y.Jones, and C.Siebold (2009).
Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP.
  Nat Struct Mol Biol, 16, 698-703.
PDB codes: 2wfq 2wfr 2wft 2wfx 2wg3 2wg4
19019827 B.H.Luo, J.Karanicolas, L.D.Harmacek, D.Baker, and T.A.Springer (2009).
Rationally designed integrin beta3 mutants stabilized in the high affinity conformation.
  J Biol Chem, 284, 3917-3924.  
19289150 C.G.Gahmberg, S.C.Fagerholm, S.M.Nurmi, T.Chavakis, S.Marchesan, and M.Grönholm (2009).
Regulation of integrin activity and signalling.
  Biochim Biophys Acta, 1790, 431-444.  
19455709 D.Provasi, M.Murcia, B.S.Coller, and M.Filizola (2009).
Targeted molecular dynamics reveals overall common conformational changes upon hybrid domain swing-out in beta3 integrins.
  Proteins, 77, 477-489.  
20560553 J.L.Eisenberg, J.L.Piper, and M.Mrksich (2009).
Using self-assembled monolayers to model cell adhesion to the 9th and 10th type III domains of fibronectin.
  Langmuir, 25, 13942-13951.  
19778727 J.Sánchez-Cortés, and M.Mrksich (2009).
The platelet integrin alphaIIbbeta3 binds to the RGD and AGD motifs in fibrinogen.
  Chem Biol, 16, 990.  
19276170 K.Tan, M.Duquette, A.Joachimiak, and J.Lawler (2009).
The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding.
  FASEB J, 23, 2490-2501.
PDB code: 3fby
19552683 R.F.Doolittle, S.Hong, and D.Wilcox (2009).
Evolution of the fibrinogen gamma' chain: implications for the binding of factor XIII, thrombin and platelets.
  J Thromb Haemost, 7, 1431-1433.  
19111664 J.Zhu, B.H.Luo, T.Xiao, C.Zhang, N.Nishida, and T.A.Springer (2008).
Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces.
  Mol Cell, 32, 849-861.
PDB codes: 3fcs 3fcu
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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