Structural and mechanistic insights into ras association domains of phospholipase C epsilon

Roe, Mark, Bunney, Tom, Driscoll, Paul, Esposito, Diego, Gierschik, Peter, Harris, Richard, Josephs, Michelle, Katan, Matilda, Lamuño Gandarillas, Natalia, Paterson, Hugh, Pearl, Laurence, Ponting, Chris, Rodrigues-Lima, Fernando and Sorli, S Caroline (2006) Structural and mechanistic insights into ras association domains of phospholipase C epsilon. Molecular Cell, 21 (4). pp. 495-507. ISSN 1097-2765

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Ras proteins signal to a number of distinct pathways by interacting with diverse effectors. Studies of ras/effector interactions have focused on three classes, Raf kinases, ral guanylnucleotide-exchange factors, and phosphatidylinositol-3-kinases. Here we describe ras interactions with another effector, the recently identified phospholipase C epsilon (PLCepsilon). We solved structures of PLCepsilon RA domains (RA1 and RA2) by NMR and the structure of the RA2/ras complex by X-ray crystallography. Although the similarity between ubiquitin-like folds of RA1 and RA2 proves that they are homologs, only RA2 can bind ras. Some of the features of the RA2/ras interface are unique to PLCepsilon, while the ability to make contacts with both switch I and II regions of ras is shared only with phosphatidylinositol-3-kinase. Studies of PLCepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCepsilon, has a role in membrane targeting with further regulatory impact on PLC activity.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Mark Roe
Date Deposited: 06 Feb 2012 19:27
Last Modified: 16 Jul 2012 13:03
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