2kig | pdb_00002kig
A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolism
Structural highlights
Function[I5P2_MOUSE] Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.[1] [2] Publication Abstract from PubMedOCRL, whose mutations are responsible for Lowe syndrome and Dent disease, and INPP5B are two similar proteins comprising a central inositol 5-phosphatase domain followed by an ASH and a RhoGAP-like domain. Their divergent NH2-terminal portions remain uncharacterized. We show that the NH2-terminal region of OCRL, but not of INPP5B, binds clathrin heavy chain. OCRL, which in contrast to INPP5B visits late stage endocytic clathrin-coated pits, was earlier shown to contain another binding site for clathrin in its COOH-terminal region. NMR structure determination further reveals that despite their primary sequence dissimilarity, the NH2-terminal portions of both OCRL and INPP5B contain a PH domain. The novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.,Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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