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

Trends Biochem Sci. 2015 Dec;40(12):736-748. doi: 10.1016/j.tibs.2015.09.007. Epub 2015 Nov 3.

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.

Keywords: BCL-2 family; BH3; MoRF/MoRE; SLiM; globular domains; intrinsically disordered proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • BH3 Interacting Domain Death Agonist Protein / chemistry*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Humans
  • Models, Molecular
  • Protein Conformation

Substances

  • BH3 Interacting Domain Death Agonist Protein