2KIG

A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolism

Summary for 2KIG

• Entry DOI: 10.2210/pdb2kig/pdb
• NMR Information: BMRB: 16273
• Descriptor: Inositol polyphosphate 5-phosphatase II isoform (1 entity in total)
• Functional Keywords: ocrl, inpp5b, ph, clathrin, endocytosis, hydrolase
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 18005.20

Authors

Mao, Y.,Hodsdon, M.E.,De Camilli, P. (deposition date: 2009-05-03, release date: 2009-06-30, Last modification date: 2024-05-22)

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

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: 19536138
DOI: 10.1038/emboj.2009.155

Experimental method

SOLUTION NMR