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[[Image:1gwb.gif|left|200px]]<br />
<applet load="1gwb" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1gwb, resolution 2.8&Aring;" />
'''STRUCTURE OF GLYCOPROTEIN 1B'''<br />


==Overview==
==STRUCTURE OF GLYCOPROTEIN 1B==
Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in, mediating the arrest of platelets at sites of vascular damage. GPIb binds, to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a, thrombus. To investigate the molecular basis of GPIb regulation and ligand, binding, we have determined the structure of the N-terminal domain of the, GPIb(alpha) chain (residues 1-279). This structure is the first determined, from the cell adhesion/signaling class of leucine-rich repeat (LRR), proteins and reveals the topology of the characteristic disulfide-bonded, flanking regions. The fold consists of an N-terminal beta-hairpin, eight, leucine-rich repeats, a disulfide-bonded loop, and a C-terminal ... [[http://ispc.weizmann.ac.il/pmbin/getpm?12087105 (full description)]]
<StructureSection load='1gwb' size='340' side='right'caption='[[1gwb]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1gwb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GWB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gwb OCA], [https://pdbe.org/1gwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gwb RCSB], [https://www.ebi.ac.uk/pdbsum/1gwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gwb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[https://omim.org/entry/258660 258660]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref>  Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[https://omim.org/entry/231200 231200]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref>  Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[https://omim.org/entry/153670 153670]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref>  Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[https://omim.org/entry/177820 177820]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref>
== Function ==
[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/1gwb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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=1gwb ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1GWB is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with NAG, NDG, PT, SO4 and ACY as [[http://en.wikipedia.org/wiki/ligands ligands]]. Structure known Active Site: AC2. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GWB OCA]].
*[[Platelet glycoprotein|Platelet glycoprotein]]
 
== References ==
==Reference==
<references/>
Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation., Uff S, Clemetson JM, Harrison T, Clemetson KJ, Emsley J, J Biol Chem. 2002 Sep 20;277(38):35657-63. Epub 2002 Jun 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12087105 12087105]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Clemetson, J.]]
[[Category: Clemetson JM]]
[[Category: Clemetson, K.]]
[[Category: Clemetson KJM]]
[[Category: Emsley, J.]]
[[Category: Emsley J]]
[[Category: Harrison, T.]]
[[Category: Harrison T]]
[[Category: Uff, S.]]
[[Category: Uff S]]
[[Category: ACY]]
[[Category: NAG]]
[[Category: NDG]]
[[Category: PT]]
[[Category: SO4]]
[[Category: bernard soulier syndrome]]
[[Category: blood coagulation]]
[[Category: cell adhesion]]
[[Category: disease mutation]]
[[Category: glycoprotein]]
[[Category: glycoprotein 1b]]
[[Category: hemostasis]]
[[Category: leucine-rich repeat]]
[[Category: platelet]]
[[Category: polymorphism]]
[[Category: repeat]]
[[Category: signal]]
[[Category: transmembrane]]
[[Category: von willebrand disease]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 08:33:26 2007''

Latest revision as of 14:24, 27 March 2024

STRUCTURE OF GLYCOPROTEIN 1BSTRUCTURE OF GLYCOPROTEIN 1B

Structural highlights

1gwb is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GP1BA_HUMAN Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:258660. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.[1] Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:231200; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.[2] [3] [4] [5] [6] [7] Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:153670; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.[8] Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:177820. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.[9] [10] [11] [12]

Function

GP1BA_HUMAN GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.

Evolutionary Conservation

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

See Also

References

  1. ↑ Salomon O, Rosenberg N, Steinberg DM, Huna-Baron R, Moisseiev J, Dardik R, Goldan O, Kurtz S, Ifrah A, Seligsohn U. Nonarteritic anterior ischemic optic neuropathy is associated with a specific platelet polymorphism located on the glycoprotein Ibalpha gene. Ophthalmology. 2004 Jan;111(1):184-8. PMID:14711733 doi:10.1016/j.ophtha.2003.05.006
  2. ↑ Miller JL, Lyle VA, Cunningham D. Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease. Blood. 1992 Jan 15;79(2):439-46. PMID:1730088
  3. ↑ Ware J, Russell SR, Marchese P, Murata M, Mazzucato M, De Marco L, Ruggeri ZM. Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome. J Clin Invest. 1993 Sep;92(3):1213-20. PMID:7690774 doi:http://dx.doi.org/10.1172/JCI116692
  4. ↑ Simsek S, Noris P, Lozano M, Pico M, von dem Borne AE, Ribera A, Gallardo D. Cys209 Ser mutation in the platelet membrane glycoprotein Ib alpha gene is associated with Bernard-Soulier syndrome. Br J Haematol. 1994 Dec;88(4):839-44. PMID:7819107
  5. ↑ de la Salle C, Baas MJ, Lanza F, Schwartz A, Hanau D, Chevalier J, Gachet C, Briquel ME, Cazenave JP. A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I). Br J Haematol. 1995 Feb;89(2):386-96. PMID:7873390
  6. ↑ Kenny D, Jonsson OG, Morateck PA, Montgomery RR. Naturally occurring mutations in glycoprotein Ibalpha that result in defective ligand binding and synthesis of a truncated protein. Blood. 1998 Jul 1;92(1):175-83. PMID:9639514
  7. ↑ Koskela S, Partanen J, Salmi TT, Kekomaki R. Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families. Eur J Haematol. 1999 Mar;62(3):160-8. PMID:10089893
  8. ↑ Savoia A, Balduini CL, Savino M, Noris P, Del Vecchio M, Perrotta S, Belletti S, Poggi, Iolascon A. Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood. 2001 Mar 1;97(5):1330-5. PMID:11222377
  9. ↑ Matsubara Y, Murata M, Sugita K, Ikeda Y. Identification of a novel point mutation in platelet glycoprotein Ibalpha, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. J Thromb Haemost. 2003 Oct;1(10):2198-205. PMID:14521605
  10. ↑ Miller JL, Cunningham D, Lyle VA, Finch CN. Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4761-5. PMID:2052556
  11. ↑ Murata M, Russell SR, Ruggeri ZM, Ware J. Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. J Clin Invest. 1993 May;91(5):2133-7. PMID:8486780 doi:http://dx.doi.org/10.1172/JCI116438
  12. ↑ Russell SD, Roth GJ. Pseudo-von Willebrand disease: a mutation in the platelet glycoprotein Ib alpha gene associated with a hyperactive surface receptor. Blood. 1993 Apr 1;81(7):1787-91. PMID:8384898

1gwb, resolution 2.80Å

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