Platelet integrin αIIbβ3-ligand interactions: What can we learn from the structure?

Tetsuji Kamata, Yoshikazu Takada

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Upon vascular injury, platelets initiate interaction with exposed subendothelial matrices through various receptors such as glycoprotein (GP) Ib/IX/V complex, α2β1 integrin, and GPVI/FcRγ. Although these interactions cannot sustain stable platelet thrombus formation by themselves, they ultimately lead to the activation of αIIbβ3 integrin (GPIIb-IIIa complex [GPIIbIIIa]), the most abundant receptor in platelets. The αIIbβ3 integrin plays a central role in primary hemostasis by serving as a receptor for fibrinogen and von Willebrand factor (vWf). It establishes a stable interaction with vWf bound to the extracellular matrices and uses fibrinogen as a bridging molecule in platelet aggregate formation. The αIIbβ3 integrin also plays an important role in the pathogenesis of thrombosis. Over the past decades, a tremendous amount of effort has been made to elucidate the ligand-binding mechanisms of αIIbβ3, in part because of its clinical significance. Most of the studies have relied on biochemical analyses of purified αIIbβ3 or recombinant proteins generated in vitro. With the lack of actual 3-dimensional structure, molecular modeling has provided a useful framework for interpreting such experimental data on structure-function correlation of integrin molecules. However, it has also generated disagreement between different models. The aim of this minireview is to summarize the past efforts as well as the recent accomplishments in elucidating the structure/function of αIIbβ3. Finally, we will try to explain all those experimental data using the recently published crystal structure of the extra cellular domains of the αVβ3 heterodimeric complex.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalInternational Journal of Hematology
Volume74
Issue number4
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • αIIbβ3
  • β-propeller
  • Fibrinogen
  • Integrin
  • Platelet

ASJC Scopus subject areas

  • Hematology

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