Identification and in silico analysis of a new group of double-histone fold-containing proteins.
The double-histone fold is a rare protein fold in which two consecutive regions characterized by the typical structure of histones assemble together, thus giving a histone pseudodimer. Previously, this fold was found in a few prokaryotic histones and in the regulatory region of guanine-nucleotide exchange factors of the Sos family. Standard methods of sequence comparison did not allow us to find new proteins containing a histone pseudodimer, as previously reported (Sondermann et al. 2003). However, a deeper investigation of protein sequences showed that the two histone folds included in Sos proteins share significant sequence similarity with nucleosomal histones. On the basis of this observation, we applied a specific strategy of sequence-homology search, which led to the identification of a new group of histone pseudodimers in Cca3 and proteins similar to Cca3 (Cca3S). A homology model of the histone pseudodimer included in rat Cca3 was constructed. A subsequent structure-function relationship study revealed that the histone pseudodimers included in Cca3 and Cca3S proteins, but not those present in Sos proteins, could retain the ability of mediating protein-DNA interactions, and could consequently act as DNA-binding modules.
Greco
Claudio
C
Dipartimento di Biotecnologie e Bioscienze, Università degli Studi Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy.
Sacco
Elena
E
Vanoni
Marco
M
De Gioia
Luca
L
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D017124:Conserved Sequence; D019281:Dimerization; D006657:Histones / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D020837:SOS1 Protein / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity; D040681:Structural Homology, Protein
D002352:Carrier Proteins; D006657:Histones; D020837:SOS1 Protein