Structure of a novel extracellular Ca(2+)-binding module in BM-40.
The EF-hand is a highly conserved Ca(2+)-binding motif found in many cytosolic Ca(2+)-modulated proteins. Here we report the crystal structure at 2.0 A resolution of the carboxy-terminal domain of human BM-40 (SPARC, osteonectin), an extracellular matrix protein containing an EF-hand pair. The two EF-hands interact canonically but their detailed structures are unusual. In the first EF-hand a one-residue insertion is accommodated by a cis-peptide bond and by substituting a carboxylate by a peptide carbonyl as a Ca2+ ligand. The second EF-hand is stabilized by a disulphide bond. The EF-hand pair interacts tightly with an amphiphilic amino-terminal helix, reminiscent of target peptide binding by calmodulin. The present structure defines a novel protein module occurring in several other extracellular proteins.
Hohenester
E
E
Department of Structural Biology, University of Basel, Switzerland.
Maurer
P
P
Hohenadl
C
C
Timpl
R
R
Jansonius
J N
JN
Engel
J
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D015676:Osteonectin / Q000378:metabolism*; D011487:Protein Conformation
D002135:Calcium-Binding Proteins; D015676:Osteonectin; D002118:Calcium