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Identification and in silico analysis of a new group of double-histone fold-containing proteins

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Abstract

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.

a and b Graphical representation of the statistical parameters (Pscore and Parea, see [20]) on which the prediction of DNA-binding site is based. Black crosses indicate the Pscore and Parea values calculated for 63 representative dsDNA-binding proteins, while the red asterisks refer to the values of the same parameters for Cca3 histone pseudodimer model (a), and for the amino-terminal domain of hSos1 (b). Only the proteins with Pscore > 0.12 and Parea > 250 (thus included in the upper right region of the graph) are considered dsDNA-binding proteins. c Localization of the predicted DNA-binding surface (in blue) on the rat Cca3 model

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Abbreviations

Cca3:

Confluent

3Y1:

Cell-associated

hSos1:

Human Son of Sevenless 1

Hs:

Homo sapiens

Mm:

Mus musculus

Rn:

Rattus norvegicus

Tn:

Tetraodon nigroviridis

Fr:

Fugu rubripes

Xt:

Xenopus tropicalis

Xl:

Xenopus laevis

Dm:

Drosophila melanogaster

Ag:

Anopheles gambiae

Ce:

Caenorhabditis elegans

Nr:

Non-redundant

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Acknowledgements

M.V. thanks MIUR-FAR for financial support. E.S. was supported by a FIRC fellowship.

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Authors and Affiliations

  1. Dipartimento di Biotecnologie e Bioscienze, Università degli Studi Milano-Bicocca, P.zza della Scienza 2, 20126, Milano, Italy

    Claudio Greco, Elena Sacco, Marco Vanoni & Luca De Gioia

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  1. Claudio Greco
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  2. Elena Sacco
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  3. Marco Vanoni
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  4. Luca De Gioia
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Corresponding authors

Correspondence to Marco Vanoni or Luca De Gioia.

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Greco, C., Sacco, E., Vanoni, M. et al. Identification and in silico analysis of a new group of double-histone fold-containing proteins. J Mol Model 12, 76–84 (2005). https://doi.org/10.1007/s00894-005-0008-8

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  • DOI: https://doi.org/10.1007/s00894-005-0008-8

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