Platelet integrin GPIIb/IIIa: structure-function correlations. An update and lessons from other integrins

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• The glycoprotein (GP) IIb/IIIa complex, also known as integrin alphaIIbbeta3, is the most abundant platelet receptor.
• It functions as an inducible receptor for adhesive proteins and is extensively studied within the integrin family.

Purpose of the Study:

• To provide an updated summary of recent (1995-1998) functional and structural data for GP IIb/IIIa and other integrins.
• To present an emerging model for the structure and bidirectional signaling mechanism of integrin alphaIIbbeta3.

Main Methods:

• Analysis of crystal structures of isolated integrin I domains.
• Integration of biochemical, mutagenesis, and modeling data.
• Review of recent experimental evidence on integrin structure-function correlations.

Main Results:

• Significant progress has been made in elucidating the major global structural features of GP IIb/IIIa.
• Crystal structures of isolated integrin I domains have been determined.
• A framework for interpreting structure-function relationships is emerging, despite the lack of a complete high-resolution structure.

Conclusions:

• Recent structural and functional data provide a basis for understanding integrin alphaIIbbeta3.
• The emerging model aids in interpreting experimental evidence and guiding future research on integrin structure and signaling.