Von Willebrand factor type A domain

Last updated
von Willebrand factor type A domain
PDB 1lfa EBI.jpg
Structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin. [1]
Identifiers
SymbolVWA
Pfam PF00092
Pfam clan CL0128
InterPro IPR002035
SCOP2 1lfa / SCOPe / SUPFAM
CDD cd00198
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1shu X:44-213 1tzn i:44-213 1sht X:44-213

1t6b Y:44-212 1rrk A:270-468 1rs0 A:270-468 1q0p A:270-468 1rtk A:270-468 1qc5 A:172-331 1pt6 A:172-338 1qcy A:172-333 1ck4 B:172-355 1mhp B:172-355 1dzi A:174-355 1aox A:174-361 1v7p C:174-361 1pqb A:174-361 1ao3 B:1691-1864 1atz B:1691-1864 1fe8 C:1691-1864 2adf A:1691-1864 1n9z A:150-328 1bho 1:150-328 1bhq 2:150-328 1idn 2:150-328 1ido :150-328 1jlm :150-328 1mf7 A:150-328 1na5 A:150-328 1m1u A:150-328 1n3y A:151-329 1mq9 A:156-327 1cqp A:156-327 1xdd B:156-327 1dgq A:156-327 1lfa A:156-327 1xuo A:156-327 1zon :156-327 1mq8 B:156-327 1ij4 L:156-327 1rd4 C:156-327 1mqa A:156-327 1zoo B:156-327 1xdg B:156-327 1zop B:156-327 1mjn A:156-327 1t0p A:156-326 1ijb A:1277-1457 1m10 A:1277-1457 1sq0 A:1277-1457 1ijk A:1277-1457 1auq :1277-1457 1u0n A:1277-1457 1uex C:1277-1457

Contents

1oak A:1277-1457 1fns A:1277-1457 1u0o C:1277-1453

The von Willebrand factor type A (vWA) domain is a protein domain named after its occurrence in von Willebrand factor (vWF), a large multimeric glycoprotein found in blood plasma. Mutant forms of vWF are involved in the aetiology of bleeding disorders. [2] This type A domain is the prototype for a protein superfamily (InterPro :  IPR036465 ; see also Pfam clan).

The vWA 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. [3] [4] [5] 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 vWA 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. [3] A number of human diseases arise from mutations in vWA domains.

Secondary structure prediction from 75 aligned vWA sequences has revealed a largely alternating sequence of alpha-helices and beta-strands. [4] Fold recognition algorithms were used to score sequence compatibility with a library of known structures: the vWA domain fold was predicted to be a doubly wound, open, twisted beta-sheet flanked by alpha-helices. [6] 3D structures have been determined for the I-domains of integrins CD11b (with bound magnesium) [7] and CD11a (with bound manganese). [8] 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. [7] 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. [8]

Human proteins containing this domain

ANTXR1; ANTXR2; BF; C2; CACHD1; CACNA2D1; CACNA2D2; CACNA2D3; CACNA2D4; CFB; CLCA1; CLCA2; CLCA4; COCH; COL12A1; COL14A1; COL20A1; COL21A1; COL22A1; COL28; COL6A1; COL6A2; COL6A3; COL7A1; COLA1L; CaCC1; ITGA1; ITGA10; ITGA11; ITGA2; ITGAD; ITGAE; ITGAL; ITGAM; ITGAX; ITIH1; ITIH2; ITIH3; ITIH4; ITIH5; ITIH5L; LOC285929; LOC340267; LOC389462; LOH11CR2A; MATN1; MATN2; MATN3; MATN4; PARP4; SVEP1（SEL-OB）; VIT; VWA1; VWA2; VWF; hCLCA1; hCLCA2; CMG2;

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References

  1. ↑ Qu A, Leahy DJ (October 1995). "Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10277–81. Bibcode:1995PNAS...9210277Q. doi: 10.1073/pnas.92.22.10277 . PMC   40779 . PMID   7479767.
  2. ↑ Ruggeri ZM, Ware J (1993). "von Willebrand factor". FASEB J. 7 (2): 308–316. doi: 10.1096/fasebj.7.2.8440408 . PMID   8440408. S2CID   10574567.
  3. 1 2 Colombatti A, Bonaldo P, Doliana R (1993). "Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins". Matrix. 13 (4): 297–306. doi:10.1016/S0934-8832(11)80025-9. PMID   8412987.
  4. 1 2 Smith KF, Haris PI, Chapman D, Perkins SJ, Williams SC, Sim RB (1994). "The secondary structure of the von Willebrand factor type A domain in factor B of human complement by Fourier transform infrared spectroscopy. Its occurrence in collagen types VI, VII, XII and XIV, the integrins and other proteins by averaged structure predictions". J. Mol. Biol. 238 (1): 104–119. doi:10.1006/jmbi.1994.1271. PMID   8145250.
  5. ↑ Bork P (1991). "Shuffled domains in extracellular proteins". FEBS Lett. 286 (1): 47–54. doi: 10.1016/0014-5793(91)80937-X . PMID   1864378. S2CID   22126481.
  6. ↑ Perkins SJ, Edwards YJ (1995). "The protein fold of the von Willebrand factor type A domain is predicted to be similar to the open twisted beta-sheet flanked by alpha-helices found in human ras-p21". FEBS Lett. 358 (3): 283–286. doi: 10.1016/0014-5793(94)01447-9 . PMID   7843416. S2CID   85317759.
  7. 1 2 Lee JO, Rieu P, Arnaout MA, Liddington R (1995). "Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18)". Cell. 80 (4): 631–638. doi: 10.1016/0092-8674(95)90517-0 . PMID   7867070. S2CID   11275359.
  8. 1 2 Leahy DJ, Qu A (1995). "Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10277–10281. Bibcode:1995PNAS...9210277Q. doi: 10.1073/pnas.92.22.10277 . PMC   40779 . PMID   7479767.
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