|PROSITE documentation PDOC51505|
SAGA (Spt-Ada-Gcn5 acetyltransferase), a coactivator complex involved in chromatin remodelling, harbors both histone acetylation and deubiquitination activities. ATXN7/Sgf73 and ATXN7L3, two subunits of the SAGA deubiquitination module, contain an ~50-residue SCA7 domain characterized by an atypical zinc-finger (ZnF) with a Cys-X(9,10)-Cys-X(5)-Cys-X(2)-His motif, which is characterized by a long sequence insertion between the first two zinc coordinating residues. The SCA7 domain is found exclusively in members of the ATXN7 gene family, which includes two distinct subunits of SAGA complexes: ATXN7 and ATXN7L3 orthologues. The analysis of multiple alignments highlights the consensus signature for the SCA7 domain, encompassing the putative zinc-coordinating residues, but also reveals the distinct features of the two proteins. Marked differences are found mostly in the carboxy-terminal of the domain, suggesting that divergent evolution of the SCA7 Znf domain occured in order to achieve specific functions in the SAGA complex. Both SCA7 domains contain disordered regions, albeit not in the same region. Whereas the first and last 10 residues of ATXN7-SCA7 (see <PDB:2KKR>) are not folded, the N-terminal region of ATXN7L3-SCA7 (see <PDB:2KKT>) is well structured and the last 30 residues of this domain are not folded. In both ATXN7-SCA7 and ATXN7L3-SCA7, the large sequence insertion between the first and second zinc-coordinating cysteines corresponds to a protruding extended hairpin structure. The core of the zinc-binding sites shows a conserved structure formed by two short adjacent loops located at the bottom of the hairpin. Although the SCA7 domains of both ATXN7 and ATXN7L3 contain two α-helices, these are not located at similar positions in the sequences. In ATXN7-SCA7, the two α-helices are located downstream from the zinc-binding site and are separated by a loop containing a large number of positively charged residues. In ATXN7L3-SCA7, the two helices lie to either side of the zinc-binding site, leading to a different packing of the two helices. In ATXN7-SCA7, the two helices have an almost perpendicular orientation, the α2 helix being anchored to the zinc-binding site. In ATXN7L3-SCA7, the helices α1 and α2 adopt an anti-parallel orientation defined by hydrophobic interactions. The ATXN7-SCA7 domain binds to the core or the C-terminal ends of the histone H2A and H2B dimer, a region located on the lateral face of the nucleosome that contains the ubiquitinated Lys 120 of H2B. This property is lost in the ATXN7-SCA7 domain [1,2].
The profile we developed covers the entire SCA7 domain.Last update:
July 2010 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||McMahon S.J. Pray-Grant M.G. Schieltz D. Yates J.R. III Grant P.A.|
|Title||Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 102:8478-8482(2005).|
|2||Authors||Bonnet J. Wang Y.-H. Spedale G. Atkinson R.A. Romier C. Hamiche A. Pijnappel W.W.M.P. Timmers H.T.M. Tora L. Devys D. Kieffer B.|
|Title||The structural plasticity of SCA7 domains defines their differential nucleosome-binding properties.|
|Source||EMBO Rep. 0:0-0(2010).|