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PDBsum entry 4z7n
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Membrane protein/immune system
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PDB id
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4z7n
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Contents |
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455 a.a.
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464 a.a.
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216 a.a.
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214 a.a.
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PDB id:
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| Name: |
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Membrane protein/immune system
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Title:
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Integrin alphaiibbeta3 in complex with agdv peptide
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Structure:
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Integrin alpha-iib. Chain: a, c. Fragment: unp residues 32-486. Synonym: gpalpha iib,gpiib,platelet membrane glycoprotein iib. Engineered: yes. Integrin beta-3. Chain: b, d. Fragment: unp residues 29-497. Synonym: platelet membrane glycoprotein iiia,gpiiia.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: itga2b, gp2b, itgab. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: itgb3, gp3a. Mus musculus. Organism_taxid: 10090.
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Resolution:
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2.60Å
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R-factor:
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0.230
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R-free:
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0.253
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Authors:
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F.-Y.Lin,J.Zhu,T.A.Springer
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Key ref:
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F.Y.Lin
et al.
(2016).
β-Subunit Binding Is Sufficient for Ligands to Open the Integrin αIIbβ3 Headpiece.
J Biol Chem,
291,
4537-4546.
PubMed id:
DOI:
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Date:
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07-Apr-15
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Release date:
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16-Dec-15
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PROCHECK
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Headers
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References
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P08514
(ITA2B_HUMAN) -
Integrin alpha-IIb from Homo sapiens
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Seq:
Struc:
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1039 a.a.
455 a.a.
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P05106
(ITB3_HUMAN) -
Integrin beta-3 from Homo sapiens
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Seq:
Struc:
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788 a.a.
464 a.a.
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DOI no:
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J Biol Chem
291:4537-4546
(2016)
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PubMed id:
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β-Subunit Binding Is Sufficient for Ligands to Open the Integrin αIIbβ3 Headpiece.
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F.Y.Lin,
J.Zhu,
E.T.Eng,
N.E.Hudson,
T.A.Springer.
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ABSTRACT
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The platelet integrin αIIbβ3 binds to a KQAGDV motif at the fibrinogen
γ-chain C terminus and to RGD motifs present in loops in many extracellular
matrix proteins. These ligands bind in a groove between the integrin α and
β-subunits; the basic Lys or Arg side chain hydrogen bonds to the
αIIb-subunit, and the acidic Asp side chain coordinates to a metal ion held by
the β3-subunit. Ligand binding induces headpiece opening, with conformational
change in the β-subunit. During this opening, RGD slides in the ligand-binding
pocket toward αIIb, with movement of the βI-domain β1-α1 loop toward αIIb,
enabling formation of direct, charged hydrogen bonds between the Arg side chain
and αIIb. Here we test whether ligand interactions with β3 suffice for stable
ligand binding and headpiece opening. We find that the AGDV tetrapeptide from
KQAGDV binds to the αIIbβ3 headpiece with affinity comparable with the RGDSP
peptide from fibronectin. AGDV induced complete headpiece opening in solution as
shown by increase in hydrodynamic radius. Soaking of AGDV into closed αIIbβ3
headpiece crystals induced intermediate states similarly to RGDSP. AGDV has very
little contact with the α-subunit. Furthermore, as measured by epitope
exposure, AGDV, like the fibrinogen γ C-terminal peptide and RGD, caused
integrin extension on the cell surface. Thus, pushing by the β3-subunit on Asp
is sufficient for headpiece opening and ligand sliding, and no pulling by the
αIIb subunit on Arg is required.
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