Linked Life Data

9803314

Source:http://linkedlifedata.com/resource/pubmed/id/9803314

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-1-8
pubmed:abstractText
S100 proteins are a family of small dimeric proteins characterized by two EF hand type Ca2+ binding motifs which are flanked by unique N- and C-terminal regions. Although shown unequivocally in only a few cases S100 proteins are thought to function by binding to, and thereby regulating, cellular target proteins in a Ca2+ dependent manner. To describe for one member of the family, S100A1, structural requirements underlying target protein binding, we generated specifically mutated S100A1 derivatives and characterized their interaction with the alpha subunit of the actin capping protein CapZ shown here to represent a direct binding partner for S100A1. Chemical cross-linking, ligand blotting and fluorescence emission spectroscopy reveal that removal of, or mutations within, the sequence encompassing residues 88-90 in the unique C-terminal region of S100A1 interfere with binding to CapZ alpha and to TRTK-12, a synthetic CapZ alpha peptide. The S100A1 sequence identified contains a cluster of three hydrophobic residues (Phe-88, Phe-89 and Trp-90) at least one of which--as revealed by qualitative phenyl Sepharose binding and hydrophobic fluorescent probe spectroscopy--is exposed on the protein surface of Ca2+ bound S100A1. As homologous hydrophobic residues in the closely related S100B protein were shown by NMR spectroscopy of Ca(2+)-free S100B dimers to provide intersubunit contacts [Kilby P.M., van Eldik L.J., Roberts G.C.K. The solution structure of the bovine S100B dimer in the calcium-free state. Structure 1996; 4: 1041-1052; Drohat A.C., Amburgey J.C., Abildgaard F., Starich M.R., Baldisseri D., Weber D.J. Solution structure of rat apo-S100B (beta beta) as determined by NMR spectroscopy. Biochemistry 1996; 35: 11,577-11,588], we characterized the physical state of the various S100A1 derivatives. Analytical gel filtration and chemical cross-linking show that dimer formation is not compromised in S100A1 mutants lacking residues 88-90 or containing specific amino acid substitutions in this sequence. Thus a cluster of hydrophobic residues in the C-terminal region of S100A1 is essential for target protein binding but dispensable for dimerization, a situation possibly met in other S100 proteins as well.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0143-4160
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Hydrophobic residues in the C-terminal region of S100A1 are essential for target protein binding but not for dimerization.
pubmed:affiliation
Institute for Medical Biochemistry, ZMBE, University of Muenster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't