GSBS Student Publications

Title

Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains

GSBS Program

Not applicable

Publication Date

2000-09-13

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate diverse cellular functions through interaction with pleckstrin homology (PH) domains in modular signaling proteins. The PH domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined the structure of the Grp1 PH domain in the unliganded form and bound to inositol 1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a 20-residue insertion within the beta6/beta7 loop explains the unusually high specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains including that of protein kinase B. When compared to other PH domains, general determinants of 3-phosphoinositide recognition and specificity can be deduced.

DOI of Published Version

10.1016/S1097-2765(00)00038-1

Source

Mol Cell. 2000 Aug;6(2):385-94.

Journal/Book/Conference Title

Molecular cell

Related Resources

Link to article in PubMed

PubMed ID

10983985

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