1mk7: Difference between revisions

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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mk/1mk7_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mk/1mk7_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mk7 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mk7 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The binding of cytoplasmic proteins, such as talin, to the cytoplasmic domains of integrin adhesion receptors mediates bidirectional signal transduction. Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin tail. The FERM (four point one, ezrin, radixin, and moesin) domain of talin engages integrins via a novel variant of the canonical phosphotyrosine binding (PTB) domain-NPxY ligand interaction that may be a prototype for FERM domain recognition of transmembrane receptors. In combination with NMR and mutational analysis, our studies reveal the critical interacting elements of both talin and the integrin beta 3 tail, providing structural paradigms for integrin linkage to the cell interior.
Structural determinants of integrin recognition by talin.,Garcia-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC Mol Cell. 2003 Jan;11(1):49-58. PMID:12535520<ref>PMID:12535520</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1mk7" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 07:43, 17 October 2024

CRYSTAL STRUCTURE OF AN INTEGRIN BETA3-TALIN CHIMERACRYSTAL STRUCTURE OF AN INTEGRIN BETA3-TALIN CHIMERA

Structural highlights

1mk7 is a 4 chain structure with sequence from Gallus gallus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ITB3_HUMAN Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:273800; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

Function

ITB3_HUMAN Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 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. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The binding of cytoplasmic proteins, such as talin, to the cytoplasmic domains of integrin adhesion receptors mediates bidirectional signal transduction. Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin tail. The FERM (four point one, ezrin, radixin, and moesin) domain of talin engages integrins via a novel variant of the canonical phosphotyrosine binding (PTB) domain-NPxY ligand interaction that may be a prototype for FERM domain recognition of transmembrane receptors. In combination with NMR and mutational analysis, our studies reveal the critical interacting elements of both talin and the integrin beta 3 tail, providing structural paradigms for integrin linkage to the cell interior.

Structural determinants of integrin recognition by talin.,Garcia-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC Mol Cell. 2003 Jan;11(1):49-58. PMID:12535520[18]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Loftus JC, O'Toole TE, Plow EF, Glass A, Frelinger AL 3rd, Ginsberg MH. A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science. 1990 Aug 24;249(4971):915-8. PMID:2392682
  2. ↑ Bajt ML, Ginsberg MH, Frelinger AL 3rd, Berndt MC, Loftus JC. A spontaneous mutation of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) helps define a ligand binding site. J Biol Chem. 1992 Feb 25;267(6):3789-94. PMID:1371279
  3. ↑ Lanza F, Stierle A, Fournier D, Morales M, Andre G, Nurden AT, Cazenave JP. A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation. J Clin Invest. 1992 Jun;89(6):1995-2004. PMID:1602006 doi:http://dx.doi.org/10.1172/JCI115808
  4. ↑ Chen YP, Djaffar I, Pidard D, Steiner B, Cieutat AM, Caen JP, Rosa JP. Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10169-73. PMID:1438206
  5. ↑ Grimaldi CM, Chen F, Scudder LE, Coller BS, French DL. A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia. Blood. 1996 Sep 1;88(5):1666-75. PMID:8781422
  6. ↑ Basani RB, Brown DL, Vilaire G, Bennett JS, Poncz M. A Leu117-->Trp mutation within the RGD-peptide cross-linking region of beta3 results in Glanzmann thrombasthenia by preventing alphaIIb beta3 export to the platelet surface. Blood. 1997 Oct 15;90(8):3082-8. PMID:9376589
  7. ↑ French DL, Coller BS. Hematologically important mutations: Glanzmann thrombasthenia. Blood Cells Mol Dis. 1997;23(1):39-51. PMID:9215749 doi:10.1006/bcmd.1997.0117
  8. ↑ Ambo H, Kamata T, Handa M, Taki M, Kuwajima M, Kawai Y, Oda A, Murata M, Takada Y, Watanabe K, Ikeda Y. Three novel integrin beta3 subunit missense mutations (H280P, C560F, and G579S) in thrombasthenia, including one (H280P) prevalent in Japanese patients. Biochem Biophys Res Commun. 1998 Oct 29;251(3):763-8. PMID:9790984 doi:10.1006/bbrc.1998.9526
  9. ↑ Jackson DE, White MM, Jennings LK, Newman PJ. A Ser162-->Leu mutation within glycoprotein (GP) IIIa (integrin beta3) results in an unstable alphaIIbbeta3 complex that retains partial function in a novel form of type II Glanzmann thrombasthenia. Thromb Haemost. 1998 Jul;80(1):42-8. PMID:9684783
  10. ↑ Ruan J, Schmugge M, Clemetson KJ, Cazes E, Combrie R, Bourre F, Nurden AT. Homozygous Cys542-->Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia. Br J Haematol. 1999 May;105(2):523-31. PMID:10233432
  11. ↑ Ruiz C, Liu CY, Sun QH, Sigaud-Fiks M, Fressinaud E, Muller JY, Nurden P, Nurden AT, Newman PJ, Valentin N. A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in the expression of a GPIIb-IIIa (alphaIIbbeta3) integrin receptor locked in a high-affinity state and a Glanzmann thrombasthenia-like phenotype. Blood. 2001 Oct 15;98(8):2432-41. PMID:11588040
  12. ↑ Nurden AT, Ruan J, Pasquet JM, Gauthier B, Combrie R, Kunicki T, Nurden P. A novel 196Leu to Pro substitution in the beta3 subunit of the alphaIIbbeta3 integrin in a patient with a variant form of Glanzmann thrombasthenia. Platelets. 2002 Mar;13(2):101-11. PMID:11897046 doi:10.1080/09537100220122466
  13. ↑ D'Andrea G, Colaizzo D, Vecchione G, Grandone E, Di Minno G, Margaglione M. Glanzmann's thrombasthenia: identification of 19 new mutations in 30 patients. Thromb Haemost. 2002 Jun;87(6):1034-42. PMID:12083483
  14. ↑ Nair S, Li J, Mitchell WB, Mohanty D, Coller BS, French DL. Two new beta3 integrin mutations in Indian patients with Glanzmann thrombasthenia: localization of mutations affecting cysteine residues in integrin beta3. Thromb Haemost. 2002 Sep;88(3):503-9. PMID:12353082 doi:10.1267/THRO88030503
  15. ↑ Gonzalez-Manchon C, Butta N, Larrucea S, Arias-Salgado EG, Alonso S, Lopez A, Parrilla R. A variant thrombasthenic phenotype associated with compound heterozygosity of integrin beta3-subunit: (Met124Val)beta3 alters the subunit dimerization rendering a decreased number of constitutive active alphaIIbbeta3 receptors. Thromb Haemost. 2004 Dec;92(6):1377-86. PMID:15583747 doi:04121377
  16. ↑ Tanaka S, Hayashi T, Yoshimura K, Nakayama M, Fujita T, Amano T, Tani Y. Double heterozygosity for a novel missense mutation of Ile304 to Asn in addition to the missense mutation His280 to Pro in the integrin beta3 gene as a cause of the absence of platelet alphaIIbbeta3 in Glanzmann's thrombasthenia. J Thromb Haemost. 2005 Jan;3(1):68-73. PMID:15634267 doi:JTH990
  17. ↑ Nair S, Ghosh K, Shetty S, Mohanty D. Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patients. J Thromb Haemost. 2005 Mar;3(3):482-8. PMID:15748237 doi:JTH1159
  18. ↑ Garcia-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC. Structural determinants of integrin recognition by talin. Mol Cell. 2003 Jan;11(1):49-58. PMID:12535520

1mk7, resolution 2.20Å

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