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The activator of apoptosis Smac-DIABLO acts as a tetramer in solution

Eloise Mastrangelo1, Patrice Vachette2, Federica Cossu3

  • 1Dipartimento di Bioscienze, Università di Milano, Milano, Italy; CNR-IBF, Istituto di Biofisica, Milano, Italy.

Biophysical Journal
|February 5, 2015
PubMed

Insights

Smac-DIABLO protein forms a tetramer, not a dimer, and binds to inhibitor of apoptosis proteins (IAPs). This tetrameric assembly is key for Smac-DIABLO

Area of Science:

  • Molecular biology
  • Structural biology
  • Biophysics

Background:

  • Smac-DIABLO protein promotes apoptosis by binding to inhibitor of apoptosis proteins (IAPs).
  • Previous studies suggested Smac-DIABLO exists as a dimer in solution.
  • Inhibitor of apoptosis proteins (IAPs) regulate caspase activity and cell survival.

Purpose of the Study:

  • To determine the solution structure of Smac-DIABLO.
  • To investigate the complex formation between Smac-DIABLO and X-linked IAP (XIAP)-BIR2-BIR3 domains.
  • To elucidate the oligomeric state and binding stoichiometry of Smac-DIABLO.

Main Methods:

  • Extensive biophysical characterization.
  • Small-angle X-ray scattering (SAXS).

Main Results:

  • Smac-DIABLO forms a tetrameric assembly in solution.
  • The Smac-DIABLO tetramer binds two BIR2-BIR3 pairs of domains from XIAP.
  • A SAXS-based model reveals conformational flexibility in the Smac-DIABLO/XIAP complex.

Conclusions:

  • Smac-DIABLO functions as a tetramer, not a dimer.
  • The tetrameric structure facilitates simultaneous binding to multiple IAP domains.
  • Conformational flexibility may enhance Smac-DIABLO's binding efficiency to IAPs, impacting apoptosis regulation.

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