Integrin Structure and Function
Chapter 2
Integrin Structure and Function
Manakan Betsy Srichai and Roy Zent
Abstract Integrins are a large family of heterodimeric glycoprotein receptors first discovered over twenty years ago. They exist as two noncovalently bound a- and b- subunits that function as adhesion molecules and play key roles in many biological processes including actin cytoskeleton organization and transduction of intracellular signals regulating cellular functions. Integrins bind a variety of extracellular matrices including collagens and laminins. The phenotypes observed from the generation of integrin knockout mice have provided a wealth of information on the unique biological functions of specific integrin heterodimers. Structural data obtained from X-ray crystallography and nuclear magnetic resonance (NMR) have provided insight into the structural basis for integrin activation and subsequent transduction of bidirectional signals bidirectionally, important for controlling biological cellular functions. Keywords Cell-Extracellular matrix interactions • Cell signaling • Cell adhesion • Cell migration
General Introduction
Integrins are a large family of type I transmembrane heterodimeric glycoprotein receptors that function as the major metazoan receptors for cell adhesion and connect the intracellular and extracellular environments. Integrins are found in organisms ranging from sponges, corals, nematodes, and echinoderms to mammals (Burke 1999). Integrins exist as two noncovalently bound a and b subunits, which pair to form heterodimers. There are 18a and 8b known subunits which combine to form at least 24 distinct integrin heterodimers (Hynes 2002). Each heterodimer consists of a large extracellular domain which binds proteins in the extracellular environment, a single-membrane-spanning transmembrane domain, and a generally
M.B. Srichai and R. Zent (*) Department of Medicine, Cancer Biology and Cell Biology, Vanderbilt Medical Center, Nashville, TN, 37232, USA
Integrin Structure and Function
Manakan Betsy Srichai and Roy Zent
Abstract Integrins are a large family of heterodimeric glycoprotein receptors first discovered over twenty years ago. They exist as two noncovalently bound a- and b- subunits that function as adhesion molecules and play key roles in many biological processes including actin cytoskeleton organization and transduction of intracellular signals regulating cellular functions. Integrins bind a variety of extracellular matrices including collagens and laminins. The phenotypes observed from the generation of integrin knockout mice have provided a wealth of information on the unique biological functions of specific integrin heterodimers. Structural data obtained from X-ray crystallography and nuclear magnetic resonance (NMR) have provided insight into the structural basis for integrin activation and subsequent transduction of bidirectional signals bidirectionally, important for controlling biological cellular functions. Keywords Cell-Extracellular matrix interactions • Cell signaling • Cell adhesion • Cell migration
General Introduction
Integrins are a large family of type I transmembrane heterodimeric glycoprotein receptors that function as the major metazoan receptors for cell adhesion and connect the intracellular and extracellular environments. Integrins are found in organisms ranging from sponges, corals, nematodes, and echinoderms to mammals (Burke 1999). Integrins exist as two noncovalently bound a and b subunits, which pair to form heterodimers. There are 18a and 8b known subunits which combine to form at least 24 distinct integrin heterodimers (Hynes 2002). Each heterodimer consists of a large extracellular domain which binds proteins in the extracellular environment, a single-membrane-spanning transmembrane domain, and a generally
M.B. Srichai and R. Zent (*) Department of Medicine, Cancer Biology and Cell Biology, Vanderbilt Medical Center, Nashville, TN, 37232, USA
References: 39 Loh E, Qi W, Vilaire G, Bennett JS (1996) Effect of cytoplasmic domain mutations on the agoniststimulated ligand binding activity of the platelet integrin alphaIIbbeta3 41 Calalb MB, Polte TR, Hanks SK (1995) Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases