Intrinsic disorder explains diverse nuclear roles of chromatin remodeling proteins

• Chromatin remodelers, a group of proteins involved in nucleosome re-positioning and modification, have extensive range of interacting partners. They form multimeric complexes and interact with modified histones, transcription, splicing, and replication factors, DNA, RNA, and the factors related to the maintenance of chromosome structure. Such diverse range of interactions is hard to explain with the presumed highly structured form of the protein. in the current analysis, the conformations of chromatin remodelers were explored using protein disorder prediction algorithms. The study revealed that a significant proportion (p < 2.2e-16) of these proteins harbor at least one long region of intrinsic disorder (>70 aa). These unstructured regions do not exhibit any preference to the N/C terminal or middle of the protein. They do not show any significant representation in the Protein Data Bank (PDB) structure repository. Limited examples from PDB indicate direct involvement of disordered regions in binding of chromatin remodeling proteins to naked or modified DNA, histones, and other chromatin-related factors. Furthermore, intrinsic disorder seen in these proteins correlates to the presence of low sequence complexity regions (p = 1.851e-10) particularly the tandem repeats of hydrophilic and charged amino acids. This probably hints at their evolutionary origin via repeat expansion. The disordered regions may enable these proteins to reversibly bind to various interacting partners and eventually contribute to functional diversity and specialization of chromatin remodeling complexes. These could also endow combinatorial action of multiple domains within a protein. We further discuss the prominent association of intrinsic disorder with other chromatin-related proteins and its functional relevance therein. Copyright (C) 2008 John Wiley & Sons, Ltd.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

structural disorder

chromatin remodeling

histone modification

Biology

Biologi

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)