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TitleThree-dimensional reconstruction of intact human integrin αIIbβ3: new implications for activation-dependent ligand binding.
Journal, issue, pagesBlood, Vol. 122, Issue 26, Page 4165-4171, Year 2013
Publish dateDec 19, 2013
AuthorsWon-Seok Choi / William J Rice / David L Stokes / Barry S Coller /
PubMed AbstractIntegrin αIIbβ3 plays a central role in hemostasis and thrombosis. We provide the first 3-dimensional reconstruction of intact purified αIIbβ3 in a nanodisc lipid bilayer. Unlike previous models, ...Integrin αIIbβ3 plays a central role in hemostasis and thrombosis. We provide the first 3-dimensional reconstruction of intact purified αIIbβ3 in a nanodisc lipid bilayer. Unlike previous models, it shows that the ligand-binding head domain is on top, pointing away from the membrane. Moreover, unlike the crystal structure of the recombinant ectodomain, the lower legs are not parallel, straight, and adjacent. Rather, the αIIb lower leg is bent between the calf-1 and calf-2 domains and the β3 Integrin-Epidermal Growth Factor (I-EGF) 2 to 4 domains are freely coiled rather than in a cleft between the β3 headpiece and the αIIb lower leg. Our data indicate an important role for the region that links the distal calf-2 and β-tail domains to their respective transmembrane (TM) domains in transmitting the conformational changes in the TM domains associated with inside-out activation.
External linksBlood / PubMed:24136164 / PubMed Central
MethodsEM (single particle)
Resolution20.5 Å
Structure data

2281

4cak

EMDB-2281, PDB-4cak:
Three-dimensional reconstruction of intact human integrin alphaIIbbeta3 in a phospholipid bilayer nanodisc
Method: EM (single particle) / Resolution: 20.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsCELL ADHESION / INTEGRIN / SINGLE PARTICLE RECONSTRUCTION

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