Calcium-binding EGF domain

In molecular biology, the calcium-binding EGF domain is an EGF-like domain of about forty amino-acid residues found in epidermal growth factor (EGF). This domain is present in a large number of membrane-bound and extracellular, mostly animal, proteins.[1][2][3][4][5] Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N-terminus of some EGF-like domains.[6] Calcium-binding may be crucial for numerous protein-protein interactions.

Calcium-binding EGF domain
crystal structure of the human mbl-associated protein 19 (map19)
Identifiers
SymbolEGF_CA
PfamPF07645
Pfam clanCL0001
InterProIPR013091
CDDcd00054

For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid.[7] The first, third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated.[6] A conserved aromatic residue, as well as the second conserved negative residue, are thought to be involved in stabilising the calcium-binding site.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes.[6]

References
  1. Davis CG (May 1990). "The many faces of epidermal growth factor repeats". New Biol. 2 (5): 410–9. PMID 2288911.
  2. Blomquist MC, Hunt LT, Barker WC (December 1984). "Vaccinia virus 19-kilodalton protein: relationship to several mammalian proteins, including two growth factors". Proc. Natl. Acad. Sci. U.S.A. 81 (23): 7363–7. doi:10.1073/pnas.81.23.7363. PMC 392146. PMID 6334307.
  3. Barker WC, Johnson GC, Hunt LT, George DG, Tsugita A (June 1986). "[Similar domains in different proteins: detection and significance]". Tanpakushitsu Kakusan Koso (in Japanese) (29 Suppl): 54–68. PMID 3534958.
  4. Doolittle RF, Feng DF, Johnson MS (1984). "Computer-based characterization of epidermal growth factor precursor". Nature. 307 (5951): 558–60. doi:10.1038/307558a0. PMID 6607417. S2CID 4305008.
  5. Appella E, Weber IT, Blasi F (April 1988). "Structure and function of epidermal growth factor-like regions in proteins". FEBS Lett. 231 (1): 1–4. doi:10.1016/0014-5793(88)80690-2. PMID 3282918. S2CID 36825870.
  6. Selander-Sunnerhagen M, Ullner M, Persson E, Teleman O, Stenflo J, Drakenberg T (September 1992). "How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X". J. Biol. Chem. 267 (27): 19642–9. PMID 1527084.
  7. Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D (July 1995). "The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions". Cell. 82 (1): 131–41. doi:10.1016/0092-8674(95)90059-4. PMID 7606779. S2CID 8741348.
This article incorporates text from the public domain Pfam and InterPro: IPR013091
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