The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape

Biochim Biophys Acta. 2016 Jun;1858(6):1350-61. doi: 10.1016/j.bbamem.2016.03.017. Epub 2016 Mar 18.

Abstract

A novel feature of the voltage-dependent anion channel (VDAC, mitochondrial porin), is the barrel, comprising an odd number of β-strands and closed by parallel strands. Recent research has focused on the N-terminal segment, which in the available structures, resides in the lumen and is not part of the barrel. In this review, the structural data obtained from vertebrate VDAC are integrated with those from VDAC in artificial bilayers, emphasizing the array of native and tagged versions of VDAC used. The data are discussed with respect to a recent gating model (Zachariae et al. (2012) Structure 20:1-10), in which the N-terminus acts not as a gate on a stable barrel, but rather stabilizes the barrel, preventing its shift into a partially collapsed, low-conductance, closed state. Additionally, the role of the N-terminus in VDAC oligomerization, apoptosis through interactions with hexokinase and its interaction with ATP are discussed briefly.

Keywords: Mitochondrial porin; N-terminus; VDAC; Voltage gating; Voltage-dependent anion selective channel; β-Barrel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biopolymers / chemistry
  • Mammals
  • Molecular Sequence Data
  • Nucleotides / chemistry
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Voltage-Dependent Anion Channels / chemistry*
  • Voltage-Dependent Anion Channels / physiology

Substances

  • Biopolymers
  • Nucleotides
  • Voltage-Dependent Anion Channels