The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions.
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Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D
The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions.
Cell. 1995 Jul 14;82(1):131-41.
- PubMed ID
- 7606779 [ View in PubMed]
- Abstract
Various diverse extracellular proteins possess Ca(2+)-binding epidermal growth factor (EGF)-like domains, the function of which remains uncertain. We have determined, at high resolution (1.5 A), the crystal structure of such a domain, from human clotting factor IX, as a complex with Ca2+. The Ca2+ ligands form a classic pentagonal bipyramid with six ligands contributed by one polypeptide chain and the seventh supplied by a neighboring EGF-like domain. The crystal structure identifies the role of Ca2+ in maintaining the conformation of the N-terminal region of the domain, but more importantly demonstrates that Ca2+ can directly mediate protein-protein contacts. The observed crystal packing of the domains provides a plausible model for the association of multiple tandemly linked EGF-like domains in proteins such as fibrillin-1, Notch, and protein S. This model is consistent with the known functional data and suggests a general biological role for these domains.