PROSITE documentation PDOC51891 [for PROSITE entry PS51891]

CENP-V/GFA domain profile

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 center 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 β-sheet (see <PDB:1X6M>. Within this β-sheet, the strands β8, β9, and β4 form a sandwich with another triple stranded mixed β-sheet (β5, β2, β1). The interconnection between the sheets is mediated by four 3(10) helices and two α helices. The sandwich arrangement of the β-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 β3 and β4 via residues of three cysteines [3].

The profile we developed covers the entire CENP-V/GFA domain.