Membrane targeting by pleckstrin homology domains.
Pleckstrin homology (PH) domains are small modular domains that occur once, or occasionally several times, in a large variety of signalling proteins. In a number of instances, PH domains act to target their host protein to the cytosolic face of cellular membranes through an ability to associate with phosphoinositides. In this review, we discuss recent advances in our understanding of PH domain function. In particular we describe the structural aspects of how PH domains have evolved to bind various phosphoinositides, how PH domains regulate phosphoinositide-mediated association to plasma and internals membranes, and finally raise the issue of PH domains in protein:protein interactions and the allosteric regulation of their host protein.
Inositide Group, Henry Wellcome Integrated Signaling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
G E
GE
Cozier
J
J
Carlton
D
D
Bouyoucef
P J
PJ
Cullen
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D001798:Blood Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; C039077:platelet protein P47