Molecular Biophysics
Tubulin Tail Sequences and Post-translational Modifications Regulate Closure of Mitochondrial Voltage-dependent Anion Channel (VDAC)
Background: Tubulin C-terminal tail (CTT) peptides bind and block VDAC.Results: CTT-albumin chimeras show that a single CTT suffices for VDAC blockade and that CTTs differ in potency by more than an order of magnitude.Conclusion: Small sequence changes or post-translational modifications in CTT result in substantial changes in VDAC blockage.Significance: Disordered protein tails are not just charged strings, but embody nuanced interaction specificity.Evidence of Distinct Channel Conformations and Substrate Binding Affinities for the Mitochondrial Outer Membrane Protein Translocase Pore Tom40
Background: Nearly all nascent mitochondrial proteins are transported by the translocase of the outer membrane (TOM) complex.Results: The core Tom40 β-barrel domain exhibits four conductive levels and three distinct substrate binding affinities.Conclusion: Tom40 interactions with presequence substrates depend upon the channel's conformation.Significance: Conformational rearrangements in Tom40 may regulate substrate interactions.
