SOLUTION STRUCTURE STUDIES OF OCRL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OCRL was originally identified as the product of the gene responsible for the OculoCerebroRenal syndrome of Lowe. The Lowe syndrome is an X-linked disorder involving congenital cataracts, mental retardation, and renal Fanconi syndrome. OCRL is a multi-domain protein comprising a central inositol 5-phosphatase domain that favours PI(4,5)P2 and PI(3,4,5)P3 as substrates. This domain is flanked at its C-terminal side by an ASH and a catalytically inactive RhoGAP-like domain and an N-terminal PH domain. We recently determined the x-ray structure of the termimal ASH and RhoGAP tandem domains and the NMR structure of the N-terminal PH domian. But how the mutiple domains in OCRL are organized is still unknown. We propose to use BioSAXS methods to obtain structural information of this multi-domain containing protein in solution. With this method, we expect to distinguish between rigid and flexible regions and assess the inter domain contacts, which may be directly related to its enzymatic functions.