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Titolo:
MYRISTOYLATION DOES NOT MODULATE THE PROPERTIES OF MARCKS-RELATED PROTEIN (MRP) IN SOLUTION
Autore:
SCHLEIFF E; SCHMITZ A; MCILHINNEY RAJ; MANENTI S; VERGERES G;
Indirizzi:
UNIV BASEL,BIOCTR,DEPT BIOPHYS CHEM,KLINGELBERGSTR 70 CH-4056 BASEL SWITZERLAND UNIV BASEL,BIOCTR,DEPT BIOPHYS CHEM CH-4056 BASEL SWITZERLAND UNIV OXFORD,DEPT PHARMACOL,MRC,ANAT NEUROPHARMACOL UNIT OXFORD OX1 3TH ENGLAND HOP PURPAN,INSERM,CJF 9510 F-31059 TOULOUSE FRANCE
Titolo Testata:
The Journal of biological chemistry
fascicolo: 43, volume: 271, anno: 1996,
pagine: 26794 - 26802
SICI:
0021-9258(1996)271:43<26794:MDNMTP>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
KINASE-C SUBSTRATE; LIGHT-CHAIN KINASE; MEMBRANE ASSOCIATION; MAJOR SUBSTRATE; CALMODULIN-BINDING; DEPENDENT BINDING; BOVINE BRAIN; RAT-BRAIN; PHOSPHORYLATION; PEPTIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
E. Schleiff et al., "MYRISTOYLATION DOES NOT MODULATE THE PROPERTIES OF MARCKS-RELATED PROTEIN (MRP) IN SOLUTION", The Journal of biological chemistry, 271(43), 1996, pp. 26794-26802

Abstract

The members of the myristoylated alanine-rich C kinase Substrate (MARCKS) family ape proteins essential for brain development and phagocytosis. MARCKS proteins bind to actin filaments and calmodulin (CaM) and are phosphorylated by protein kinase C. In order to investigate how these interactions are regulated, we have characterized the properties of both the myristoylated (myr) and unmyristoylated (unmyr) forms of recombinant MARCKS-related protein (MRP), a 20-kDa member of the MARCKS family. Ultracentrifugation and circular dichroic spectroscopy reveal that MRP is an elongated protein, with an axis ratio estimated between7 and 12 and with an apparent random coil conformation, MRP binds to CaM with high affinity (K-d,K-myr = 4 nM; K-d,K-unmyr = 7 nM) and witha second order rate constant, k(+1, unmyr), of 1.6 x 10(8) M(-1) s(-1). In contrast to classical ligands such as the myosine light chain kinase, binding of MRP to CaM does not induce the formation of an alpha-helix in MRP. The catalytic subunit of protein kinase C (PKM) phosphorylates myr MRP with high affinity ([S](0.5) = 3.5 mu M), positive cooperativity (n(H) = 2.5) and a turnover number of 130 min(-1). CaM inhibits the phosphorylation of myr MRP with a half-maximum rate of phosphorylation at a [CaM]/[MRP] ratio of 0.7, indicating that CaM might efficiently regulate the phosphorylation of MRP in vivo. Interestingly, Ca2+ inhibits the binding of MRP to CaM as well as its phosphorylation by PKM in the millimolar concentration range, suggesting that MRP has aweak affinity for Ca2+. Finally, unmyr MRP can be stoichiometrically myristoylated by N-myristoyl transferase in vitro. Since neither binding of CaM nor phosphorylation by PKM inhibits myristoylation, the N terminus of unmyr MRP is exposed on the surface of the protein and is well separated from the effector domain, In view of the observations that unmyr and myr MRP do not exhibit significant differences in their properties in solution, the function of myristoylation is most probably to modulate. the interactions of MRP with membranes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 06:03:35