Redefining the BH3 Death Domain as a 'Short Linear Motif'.

TitleRedefining the BH3 Death Domain as a 'Short Linear Motif'.
Publication TypeJournal Article
Year of Publication2015
AuthorsAouacheria, A., Combet C., Tompa P., and J Hardwick M.
JournalTrends Biochem Sci
Volume40
Issue12
Pagination736-48
Date Published2015 Dec
ISSN0968-0004
KeywordsAmino Acid Motifs, Animals, BH3 Interacting Domain Death Agonist Protein, Humans, Models, Molecular, Protein Conformation
Abstract

B cell lymphoma-2 (BCL-2)-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence the BCL-2 family has expanded to include a nebulous group of nonhomologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs) and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions.

DOI10.1016/j.tibs.2015.09.007
Alternate JournalTrends Biochem. Sci.
PubMed ID26541461
PubMed Central IDPMC5056427
Grant ListDP2 NS083372 / NS / NINDS NIH HHS / United States
R01 GM077875 / GM / NIGMS NIH HHS / United States
R01 NS037402 / NS / NINDS NIH HHS / United States
R01 NS083372 / NS / NINDS NIH HHS / United States
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