3GPE

Crystal Structure Analysis of PKC (alpha)-C2 domain complexed with Ca2+ and PtdIns(4,5)P2

Summary for 3GPE

• Entry DOI: 10.2210/pdb3gpe/pdb
• Related: 1dsy 1gmi
• Descriptor: Protein kinase C alpha type, CALCIUM ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: calcium/phospholipid binding domain, c2 domain, phosphatidil serine, protein kinase, atp-binding, kinase, metal-binding, nucleotide-binding, phorbol-ester binding, phosphoprotein, serine/threonine-protein kinase, transferase, zinc-finger, signaling protein
• Biological source: Rattus norvegicus (brown rat,rat,rats)
• Cellular location: Cytoplasm: P05696
• Total number of polymer chains: 1
• Total formula weight: 17307.55

Authors

Ferrer-Orta, C.,Querol-Audi, J.,Fita, I.,Verdaguer, N. (deposition date: 2009-03-23, release date: 2009-05-05, Last modification date: 2024-04-03)

Primary citation

Guerrero-Valero, M.,Ferrer-Orta, C.,Querol-Audi, J.,Marin-Vicente, C.,Fita, I.,Gomez-Fernandez, J.C.,Verdaguer, N.,Corbalan-Garcia, S.
Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2.
Proc.Natl.Acad.Sci.USA, 106:6603-6607, 2009

PubMed Abstract: 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.

PubMed: 19346474
DOI: 10.1073/pnas.0813099106

Experimental method

X-RAY DIFFRACTION (2 Å)