PMID- 10562545
OWN - NLM
STAT- MEDLINE
DCOM- 20000120
LR  - 20131121
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 22
DP  - 1999 Nov 15
TI  - Ca(2+) bridges the C2 membrane-binding domain of protein kinase Calpha directly
      to phosphatidylserine.
PG  - 6329-38
AB  - 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.
FAU - Verdaguer, N
AU  - Verdaguer N
AD  - IBMB-CSIC, Jordi Girona Salgado 18,26, E-08034 Barcelona.
FAU - Corbalan-Garcia, S
AU  - Corbalan-Garcia S
FAU - Ochoa, W F
AU  - Ochoa WF
FAU - Fita, I
AU  - Fita I
FAU - Gomez-Fernandez, J C
AU  - Gomez-Fernandez JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (1,2-dicaproylphosphatidylserine)
RN  - 0 (Isoenzymes)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Calcium/*metabolism
MH  - Cloning, Molecular
MH  - Computer Simulation
MH  - Crystallography, X-Ray
MH  - Escherichia coli
MH  - Isoenzymes/*chemistry/*metabolism
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Phosphatidylserines/*metabolism
MH  - Protein Conformation
MH  - Protein Kinase C/*chemistry/*metabolism
MH  - Protein Kinase C-alpha
MH  - Protein Structure, Secondary
MH  - Recombinant Proteins/chemistry/metabolism
PMC - PMC1171696
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1093/emboj/18.22.6329 [doi]
PST - ppublish
SO  - EMBO J. 1999 Nov 15;18(22):6329-38. doi: 10.1093/emboj/18.22.6329.