InterPro domain: IPR006913

Centrome protein (CENP)-V is a kinetochore protein that drives the progression of mitosis by coordinating chromatin condensation, positioning of sister chromatid centromeres and targeting of the chromosome passager complex (CPC), a machinery that regulates the attachment of spindle microtubules (MTs) to kinetochores. CENP-V homologues are found in all vertebrates as well as in plants and nematodes. At the C-terminal end, CENP-V possesses an evolutionally conserved domain that comprises an array of seven cysteines and shows high structural similarity to glutathione-dependent formaldehyde-activating enzyme (Gfa), an enzyme responsible for formaldehyde detoxification in prokaryotes. CENP-V could be an enzyme that scavenges the formaldehyde produced in histone demethylation reactions. The three central cysteines and the flanking four cysteines separately coordinate to zinc, forming a catalytic centre and a structural fold for a tertiary structure, respectively [ 1 , 2 , 3 ].

The main topological feature of the CENP-V/GFA domain is an extremely twisted mixed eight-stranded beta-shee. Within this beta-sheet, the strands beta8, beta9, and beta4 form a sandwich with another triple stranded mixed beta-sheet (beta5, beta2, beta1). The interconnection between the sheets is mediated by four 3(10) helices and two alpha helices. The sandwich arrangement of the beta-strands is further buttressed by a terahedral zinc coordinated by the side chains of four cysteines. It appears that this zinc atom has only a structural role. A second zinc ion stabilizes a large hairpin loop that connects beta3 and beta4 via residues of three cysteines [ 4 ].

This entry represents the CENP-V/GFA domain.

1. CENP-V is required for centromere organization, chromosome alignment and cytokinesis. EMBO J. 27, 2510-22
2. Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction. Genes Cells 14, 1383-94
3. A dynamic zinc redox switch. J. Biol. Chem. 280, 2826-30