Nature Structural Biology
3, 67 - 73 (1996)
doi:10.1038/nsb0196-67
Structure of a novel extracellular Ca2+-binding module in BM-40Erhard Hohenester1, Patrik Maurer2, Christine Hohenadl2, Rupert Timpl2, Johan N. Jansonius1
& Jürgen Engel3
1Department of Structural Biology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland
2Max-Planck-lnstitut für Biochemie, D-82152 Martinsried, Germany
3Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland The EF-hand is a highly conserved Ca2+-binding motif found in many cytosolic Ca2+-modulated proteins. Here we report the crystal structure at 2.0 Å 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.
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