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Structural and mechanistic insights into ras association domains of phospholipase C epsilon
journal contributionposted on 2023-06-07, 22:58 authored by Mark Roe, Tom Bunney, Paul Driscoll, Diego Esposito, Peter Gierschik, Richard Harris, Michelle Josephs, Matilda Katan, Natalia Lamuño Gandarillas, Hugh Paterson, Laurence Pearl, Chris Ponting, Fernando Rodrigues-Lima, S Caroline Sorli
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.
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- Biochemistry Publications
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