Description
The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders [PubMed:8440408]. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins [PubMed:8412987], [PubMed:8145250], [PubMed:1864378]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events (e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands [PubMed:8412987]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of alpha-helices and beta-strands [PubMed:8145250]. Fold recognition algorithms were used to score sequence compatibility with a library of known structures: the vWF domain fold was predicted to be a doubly-wound, open, twisted beta-sheet flanked by alpha-helices [PubMed:7843416]. 3D structures have been determined for the I-domains of integrins CD11b (with bound magnesium) [PubMed:7867070] and CD11a (with bound manganese) [PubMed:7479767]. The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It has been suggested that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands [PubMed:7867070]. The residues constituting the MIDAS motif in the CD11b and CD11a I-domains are completely conserved, but the manner in which the metal ion is coordinated differs slightly [PubMed:7479767].
Description text from InterPro entry IPR002035
Abstracts (2):
Matrix. 1993 Jul;13(4):297-306. Related Articles, Links
Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins.
Colombatti A, Bonaldo P, Doliana R.
Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico, Aviano, Italy.
A 200-amino acid long motif first recognized in von Willebrand Factor (type A module) has been found in components of the extracellular matrix, hemostasis, cellular adhesion, and immune defense mechanisms. At present the extracellular matrix is the predominant site of expression of type A modules since at least four non-fibrillar collagens and two non-collagenous proteins contain a variable number of modules ranging from one to twelve. The modules conform to a consensus motif made of short conserved subregions separated by stretches of variable length. The proteins that incorporate type A modules participate in numerous biological events such as cell adhesion, migration, homing, pattern formation, and signal transduction after interaction with a large array of ligands.
Its Occurrence in Collagen Types VI, VII, XII and XIV, the Integrins and Other Proteins by Averaged Structure Predictions
Stephen J. Perkins, Kathryn F. Smith, Samantha C. Williams, Parvez I. Haris, Dennis Chapman and Robert B. Sim
Departments of Biochemistry and Chemistry, and Protein and Molecular Biology Royal Free Hospital School of Medicine Rowland Hill Street, London NW3 2PF, U.K. and MRC Immunochemistry Unit, Department of Biochemistry University of Oxford South Parks Road, Oxford OX1 3QU, U.K.
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) domains. 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 -helix, and at 1676 to 1685 cm-1 and 1636 to 1637 cm-1, which are typical of -strand. -Helix was detected in the vWF domain, the Bb fragment and FB, and the proportion of -helix present decreased in that order. This shows that the vWF domain contains appreciable amounts of -helix, while the SP and SCR/CCP domains are almost entirely -sheet in their secondary structures. Quantitative integration of the vWF FT-IR spectrum showed that this contained 31% -helix and 36% -sheet. In 2 H2O buffer, the -helix content in the vWF domain is sensitive to the solvent, while the -sheet content is less 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 residues by the Robson and Chou-Fasman methods. In support of the FT-IR analysis, a total of at least five well-predicted - helices (35% of residues) and at least five well-predicted -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 -helices and - strands form an alternating arrangement with each other. Since the predicted -helices are mostly amphipathic, and since the -helix FT-IR band is sensitive to solvent, the -helices are inferred to be on the protein surface. The predicted -strands are 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%) and on - helices (22%). Two Asp residues implicated in metal binding are located in two predicted hydrophilic loops just after the C- terminal end of two -strands.
Author Keywords: complement factor B; collagen type VI; integrins; FT-IR spectroscopy; secondary structure prediction