Membrane and juxtamembrane targeting by PH and PTB domains.
Modular pleckstrin homology (PH) and phospho-tyrosine binding (PTB) domains are present in a remarkably large number of proteins from yeast to humans. With a common core fold, these domain families have evolved to recognize membrane embedded phospholipids, in particular phosphoinositides, peripheral membrane proteins, and peptide motifs in juxtamembrane regions of integral membrane proteins. As the result of intensive investigation using biochemical, biophysical, and structural approaches, common ligand recognition principles have emerged along with insights into the structural variations that account for the diversity of ligand specificities. Analyses of membrane targeting in cells have revealed additional determinants beyond the primary ligand binding sites. In this review, we highlight unifying recognition principles and further illustrate with examples how divergent mechanisms contribute to membrane and juxtamembrane targeting by PH and PTB domains.
DiNitto
Jonathan P
JP
Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Two Biotech, Worcester, MA 01605, USA.
Lambright
David G
DG
D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry*; D008958:Models, Molecular; D010716:Phosphatidylinositols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics; D019000:Phosphotyrosine / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity
D001798:Blood Proteins; D010716:Phosphatidylinositols; D010743:Phospholipids; D010750:Phosphoproteins; C039077:platelet protein P47; D019000:Phosphotyrosine