Unknown

Dataset Information

0

Ca(2+) bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine.


ABSTRACT: The C2 domain acts as a membrane-targeting module in a diverse group of proteins including classical protein kinase Cs (PKCs), where it plays an essential role in activation via calcium-dependent interactions with phosphatidylserine. The three-dimensional structures of the Ca(2+)-bound forms of the PKCalpha-C2 domain both in the absence and presence of 1, 2-dicaproyl-sn-phosphatidyl-L-serine have now been determined by X-ray crystallography at 2.4 and 2.6 A resolution, respectively. In the structure of the C2 ternary complex, the glycerophosphoserine moiety of the phospholipid adopts a quasi-cyclic conformation, with the phosphoryl group directly coordinated to one of the Ca(2+) ions. Specific recognition of the phosphatidylserine is reinforced by additional hydrogen bonds and hydrophobic interactions with protein residues in the vicinity of the Ca(2+) binding region. The central feature of the PKCalpha-C2 domain structure is an eight-stranded, anti-parallel beta-barrel with a molecular topology and organization of the Ca(2+) binding region closely related to that found in PKCbeta-C2, although only two Ca(2+) ions have been located bound to the PKCalpha-C2 domain. The structural information provided by these results suggests a membrane binding mechanism of the PKCalpha-C2 domain in which calcium ions directly mediate the phosphatidylserine recognition while the calcium binding region 3 might penetrate into the phospholipid bilayer.

SUBMITTER: Verdaguer N 

PROVIDER: S-EPMC1171696 | biostudies-other | 1999 Nov

REPOSITORIES: biostudies-other

altmetric image

Publications

Ca(2+) bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine.

Verdaguer N N   Corbalan-Garcia S S   Ochoa W F WF   Fita I I   Gómez-Fernández J C JC  

The EMBO journal 19991101 22


The C2 domain acts as a membrane-targeting module in a diverse group of proteins including classical protein kinase Cs (PKCs), where it plays an essential role in activation via calcium-dependent interactions with phosphatidylserine. The three-dimensional structures of the Ca(2+)-bound forms of the PKCalpha-C2 domain both in the absence and presence of 1, 2-dicaproyl-sn-phosphatidyl-L-serine have now been determined by X-ray crystallography at 2.4 and 2.6 A resolution, respectively. In the struc  ...[more]

Similar Datasets

| S-EPMC1345646 | biostudies-literature
| S-EPMC1220004 | biostudies-other
| S-EPMC3670696 | biostudies-literature
| S-EPMC2533782 | biostudies-literature
| S-EPMC2838304 | biostudies-literature
| S-EPMC8454703 | biostudies-literature
| S-EPMC5071625 | biostudies-literature
| S-EPMC3117680 | biostudies-literature
| S-EPMC6149819 | biostudies-literature
| S-EPMC2913972 | biostudies-literature