1M1X Cell Adhesion date Jun 20, 2002
title Crystal Structure Of The Extracellular Segment Of Integrin Alpha Vbeta3 Bound To Mn2+
authors J.-P.Xiong, T.Stehle, R.Zhang, A.Joachimiak, M.Frech, S.L.Goodman, M.A.Arnaout
compound source
Molecule: Integrin Alpha-V
Chain: A
Fragment: Residues 31-987
Synonym: Vitronectin Receptor Alpha Subunit, Cd51 Antigen
Engineered: Yes
 Organism_scientific: Homo Sapiens
Organism_common: Human
Cell_line: Sf9
Expression_system: Spodoptera Frugiperda
Expression_system_common: Fall Armyworm
Expression_system_vector_type: Baculovirus

Molecule: Integrin Beta-3
Chain: B
Fragment: Residues 27-718
Synonym: Platelet Membrane Glycoprotein Iiia, Gpiiia, Cd61 Antigen;
Engineered: Yes
Organism_scientific: Homo Sapiens
Organism_common: Human
Cell_line: Sf9
Expression_system: Spodoptera Frugiperda
Expression_system_common: Fall Armyworm
Expression_system_vector_type: Baculovirus
symmetry Space Group: P 32 2 1
R_factor 0.244
crystal
cell
length a length b length c angle alpha angle beta angle gamma
130.400 130.400 310.300 90.00 90.00 120.00
method X-Ray Diffractionresolution 3.30 Å
ligand NAG, MNenzyme
similarity Contains 1 vwfa-like domain. Belongs to the integrin_Beta chain family. Belongs to the integrin alpha chain family.
subunit Beta-3 associates with either alpha-iib or alpha-v. The alpha subunit is composed of an heavy and a light chain linked by a disulfide bond. Alpha-v associates with either beta-1, beta-3, beta-5, beta-6 or beta-8 subunit. Isoform beta-3c interacts with flnb. Heterodimer of an alpha and a beta subunit.
polymorphism Position 59 is associated with platelet-specific alloantigen hpa-1 (zw or pl(a)). Position 662 is associated with platelet-specific alloantigen sr(a). Position 433 is associated with platelet-specific alloantigen mo. Ca(+) is involved in nait. Position 169 is associated with platelet-specific alloantigen hpa-4 (pen or yuk). Mo(-) has pro-433 and mo(+) has ala-433. Hpa-1a/zw(a)/pl(a1) has leu-59 and hpa-1b/zw(b)/pl(a2) has pro-59. Hpa-4a/pen(a)/yuk(a) has arg-169 and hpa-4b/pen(b)/yuk(b) has gln-169. Position 515 is associated with platelet-specific alloantigen ca/tu. Sr(a)(-) has arg-662 and sr(a)(+) has cys-662. Hpa-4b is involved in neonatal alloimmune thrombocytopenia (nait or natp). Ca(-)/tu(-) has arg-515 and ca(+)/tu(+) has gln-515. Mo(+) is involved in nait.
post-translat. modifications Shc binding also occurs when tyr-785 alone is phosphorylated. Phosphorylated on tyrosine residues in response to thrombin- induced platelet aggregation. A peptide (aa 740-762) is capable of binding grb2 only when both tyr-773 and tyr-785 are phosphorylated. Probably involved in outside-in signaling.
tissue Isoform beta-3a is specifically expressed in osteoblast cells; isoform beta-3c is specifically expressed in prostate and testis. Isoform beta-3a and isoform beta-3c are widely expressed.
subcellular loc. Type i membrane protein.
genes GP3A, ITGAV, ITGB3, VNRA (H. sapiens)
function They recognize the sequence r-g-d in a wide array of ligands. Integrin alpha-iib/beta-3 recognizes the sequence h-h-l-g-g-g-a-k-q-a-g-d-v in fibrinogen gamma chain. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Integrin alpha-v/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von willebrand factor. Integrins alpha-iib/beta-3 and alpha-v/beta-3 recognize the sequence r-g-d in a wide array of ligands. Following activation integrin alpha- iib/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. Integrin alpha-iib/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. The alpha-v integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and von willebrand factor.
Gene
Ontology 		chain A: GO:0005515, GO:0005887, GO:0007155, GO:0007160, GO:0007229, GO:0008305, GO:0016021
chain B: GO:0004872, GO:0005515, GO:0005887, GO:0007155, GO:0007160, GO:0007229, GO:0007596, GO:0008305, GO:0016021
disease Glanzmann thrombasthenia,type B
It is characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. The platelets of gt variants have normal or near normal (60-100%) expression of dysfunctional receptors. Gt has been classified clinically into types i and ii. Defects in itgb3 are a cause of glanzmann thrombasthenia (gt) [mim. 273800]; also known as thrombasthenia of glanzmann and naegeli. Its inheritance is autosomal recessive. In type i, platelets show absence of the glycoprotein iib-iiia complexes at their surface and lack fibrinogen and clot retraction capability. Gt is the most common inherited disease of platelets. In type ii, the platelets express the gpiib-iiia complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability.
Primary referenceCrystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand., Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA, Science 2002 Apr 5;296(5565):151-5. PMID:11884718
Data retrieval
  • Asymmetric unit, PDB entry: [header only] [complete with coordinates] (269 Kb) [Save to disk]
  • Biological Unit Coordinates (1m1x.pdb1.gz) 239 Kb
  • LPC: Ligand-Protein Contacts for 1M1X
  • CSU: Contacts of Structural Units for 1M1X
  • Likely Quarternary Molecular Structure file(s) for 1M1X
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  • Classification of representative domains in scop (Structural Classification of Proteins)
        - Domain d1m1xa4, region A:1-438 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xa1, region A:439-598 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xa2, region A:599-737 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xa3, region A:738-956 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xb2, region B:107-354 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xb4, region B:532-562 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xb1, region B:55-106,B:355-434 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xb5, region B:563-605 [Jmol] [rasmolscript] [script source]
        - Domain d1m1xb3, region B:606-690 [Jmol] [rasmolscript] [script source]
  • Fold representative 1m1x from FSSP and Dali (Families of Structurally Similar Proteins)
    • Sequence-derived information
  • View one-letter amino acid or nucleotide sequence for each chain: [1m1x_A] [1m1x_B]
  • SWISS-PROT database: [O15495] [P06756] [Q16499] [Q14648] [Q13413] [P05106]
  • Domain organization of [ITAV_HUMAN] [ITB3_HUMAN] by SWISSPFAM
  • Conserved protein region description, domain view and alignment from family integrin_B (PF00362) of Pfam.
  • Alignments of the sequence of 1M1X with the sequences similar proteins can be viewed for classification [ITAV_HUMAN] [ITB3_HUMAN] at ProtoMap. Click on "Neighbors List", then on the "See Alignments" button below the list.
  • A sequence distance tree ("phylogenetic tree") can be viewed for 1ACL's classification [ITAV_HUMAN] [ITB3_HUMAN] at ProtoMap. Click on the Cluster number.
    • Other resources with information on 1M1X
  • InterPro: IPR000413 , IPR003659 , IPR002035 , IPR001169 , IPR002369 , IPR006209
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