Publication Abstract from PubMed
C2 domains are widely-spread protein signaling motifs that in classical PKCs act as Ca(2+)-binding modules. However, the molecular mechanisms of their targeting process at the plasma membrane remain poorly understood. Here, the crystal structure of PKCalpha-C2 domain in complex with Ca(2+), 1,2-dihexanoyl-sn-glycero-3-[phospho-l-serine] (PtdSer), and 1,2-diayl-sn-glycero-3-[phosphoinositol-4,5-bisphosphate] [PtdIns(4,5)P(2)] shows that PtdSer binds specifically to the calcium-binding region, whereas PtdIns(4,5)P(2) occupies the concave surface of strands beta3 and beta4. Strikingly, the structure reveals a PtdIns(4,5)P(2)-C2 domain-binding mode in which the aromatic residues Tyr-195 and Trp-245 establish direct interactions with the phosphate moieties of the inositol ring. Mutations that abrogate Tyr-195 and Trp-245 recognition of PtdIns(4,5)P(2) severely impaired the ability of PKCalpha to localize to the plasma membrane. Notably, these residues are highly conserved among C2 domains of topology I, and a general mechanism of C2 domain-membrane docking mediated by PtdIns(4,5)P(2) is presented.
Structural and mechanistic insights into the association of PKC{alpha}-C2 domain to PtdIns(4,5)P2.,Guerrero-Valero M, Ferrer-Orta C, Querol-Audi J, Marin-Vicente C, Fita I, Gomez-Fernandez JC, Verdaguer N, Corbalan-Garcia S Proc Natl Acad Sci U S A. 2009 Apr 3. PMID:19346474[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
