The three‐dimensional structure of the first EGF‐like module of human factor IX: Comparison with EGF and TGF‐α

Abstract

The three‐dimensional structure of the first epidermal growth factor (EGF)‐like module from human factor IX has been determined in solution using two‐dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor‐α (TGF‐α). Residues 60–65 form an antiparallel β‐sheet with residues 68–73. In the C‐terminal subdomain a type II β‐turn is found between residues 74 and 77 and a five‐residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel β‐sheet conformation. In the N‐terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the β‐sheet. Residues 56–60 form a turn that leads into the first strand of the β‐sheet. Whereas the global fold closely resembles that of EGF, the N‐terminal residues of the module (46–49) do not form a β‐strand but are ill‐defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site‐directed mutagenesis data, which have identified certain conserved residues as ligands for calcium. Copyright © 1992 The Protein Society