The type A domain of the von Willebrand Factor is found also in the complement proteins factor B (FB), C2, CR3 and CR4, the integrins, collagen types VI, VII, XII and XIV, and other proteins. FB is a component of the alternative pathway of the complement system of immune defence, and is cleaved into the fragments Bb and Ba during complement activation. Bb contains a von Willebrand Factor type A (vWF) domain of unknown secondary structure and a serine proteinase (SP) domain, whereas Ba contains three short consensus repeat/complement control protein (SCR/CCP) domaine. Fourier transform infrared (FT-IR) spectroscopy on a recombinant vWF domain and on FB and its Bb and Ba fragments shows a broad amide I band. In H2O buffer, second derivative spectra of the amide I band show subcomponents at 1654 to 1657 cm−1, which is typical of α-helix, and at 1676 to 1685 cm-1 and 1636 to 1637cm−1, which are typical of α-strand. α-Helix was detected in the vWF domain, the Bb fragment and FB, and the proportion of α-helix present decreased in that order. This shows that the vWF domain contains appreciable amounts of α-helix, while the SP and SCR/CCP domains are almost entirely α-sheet in their secondary structures. Quantitative integration of the vWF FT-IR spectrum showed that this contained 31% α-helix and 36% α-sheet. In 2H2O buffer, the α-helix content in the vWF domain is sensitive to the solvent, while the α-sheet contentis leas so. An alignment of 75 vWF type A sequences from 25 proteins was used for averaged secondary structure predictions of the total length of 206 residuesby the Rubson and Chou-Fasman methods. In support of the FT-IR analysis, a total of at least five well-predicted α-helices (35% of residues) and at leastfive well-predicted α-strands (21% of residues) were identified by both predictive methods, all of which were interspersed by regions of coil or turn conformations. Eight of the ten predicted α-helices and α-strands form an alternating arrangement with each other. Since the predicted α-helices are mostly amphipathic, and since the α-helix FT-IR band is sensitive to solvent, the α-helices are inferred to be on the protein surface.The predicted α-strands arc hydrophobic and therefore inferred to be buried in the protein core, again in accordance with the FT-IR data. Putative glycosylation sites are found mainly in solvent-exposed positions in the predicted coil or turn regions (63%) andon α-helices (22%), Two Asp residues implicated in metal binding are located in two predicted hydrophilic loops just after the C terminal end of two α-strands. © 1994 Academic Press, Inc.