2KIE
A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolis
Summary for 2KIE
| Entry DOI | 10.2210/pdb2kie/pdb |
| NMR Information | BMRB: 16271 |
| Descriptor | Inositol polyphosphate 5-phosphatase OCRL-1 (1 entity in total) |
| Functional Keywords | ocrl, inpp5b, ph, clathrin, endocytosis, alternative splicing, cataract, disease mutation, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Endosome: Q01968 |
| Total number of polymer chains | 1 |
| Total formula weight | 13869.88 |
| Authors | Mao, Y.,Balkin, D.M.,Zoncu, R.,Erdmann, K.,Tomasini, L.,Hu, F.,Jin, M.M.,Hodsdon, M.E.,De Camilli, P. (deposition date: 2009-05-03, release date: 2009-07-21, Last modification date: 2024-11-20) |
| Primary citation | Mao, Y.,Balkin, D.M.,Zoncu, R.,Erdmann, K.S.,Tomasini, L.,Hu, F.,Jin, M.M.,Hodsdon, M.E.,De Camilli, P. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism Embo J., 28:1831-1842, 2009 Cited by PubMed Abstract: OCRL, 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. PubMed: 19536138DOI: 10.1038/emboj.2009.155 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
