The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly

J Biol Chem. 2012 Dec 21;287(52):43351-8. doi: 10.1074/jbc.M112.431270. Epub 2012 Nov 13.

Abstract

Iron-sulfur (Fe-S) clusters are essential cofactors of proteins with a wide range of biological functions. A dedicated cytosolic Fe-S cluster assembly (CIA) system is required to assemble Fe-S clusters into cytosolic and nuclear proteins. Here, we show that the mammalian nucleotide excision repair protein homolog MMS19 can simultaneously bind probable cytosolic iron-sulfur protein assembly protein CIAO1 and Fe-S proteins, confirming that MMS19 is a central protein of the CIA machinery that brings Fe-S cluster donor proteins and the receiving apoproteins into proximity. In addition, we show that mitotic spindle-associated MMXD complex subunit MIP18 also interacts with both CIAO1 and Fe-S proteins. Specifically, it binds the Fe-S cluster coordinating regions in Fe-S proteins. Furthermore, we show that ADP/ATP translocase 2 (ANT2) interacts with Fe-S apoproteins and MMS19 in the CIA complex but not with the individual proteins. Together, these results elucidate the composition and interactions within the late CIA complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotide Translocator 2 / genetics
  • Adenine Nucleotide Translocator 2 / metabolism*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoplasm / genetics
  • Cytoplasm / metabolism*
  • HEK293 Cells
  • Humans
  • Metallochaperones / genetics
  • Metallochaperones / metabolism
  • Metalloproteins
  • Mice
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding / physiology
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Adenine Nucleotide Translocator 2
  • CIAO1 protein, human
  • CIAO2B protein, human
  • Carrier Proteins
  • MMS19 protein, human
  • MMS19 protein, mouse
  • Metallochaperones
  • Metalloproteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Transcription Factors