The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A.

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TitleThe calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A.
Publication TypeJournal Article
Year of Publication2010
AuthorsGilquin, B, Cannon, BR, Hubstenberger, A, Moulouel, B, Falk, E, Merle, N, Assard, N, Kieffer, S, Rousseau, D, Wilder, PT, Weber, DJ, Baudier, J
JournalMol Cell Biol
Volume30
Issue11
Pagination2724-36
Date Published2010 Jun
ISSN1098-5549
KeywordsAdenosine Triphosphatases, Amino Acid Sequence, Animals, Calcium, Cell Line, Cytoplasm, DNA-Binding Proteins, Humans, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Nerve Growth Factors, Nuclear Magnetic Resonance, Biomolecular, Oligodendroglia, Peptides, Protein Structure, Tertiary, Rats, S100 Proteins, Sequence Alignment, Stem Cells
Abstract

S100 proteins comprise a multigene family of EF-hand calcium binding proteins that engage in multiple functions in response to cellular stress. In one case, the S100B protein has been implicated in oligodendrocyte progenitor cell (OPC) regeneration in response to demyelinating insult. In this example, we report that the mitochondrial ATAD3A protein is a major, high-affinity, and calcium-dependent S100B target protein in OPC. In OPC, ATAD3A is required for cell growth and differentiation. Molecular characterization of the S100B binding domain on ATAD3A by nuclear magnetic resonance (NMR) spectroscopy techniques defined a consensus calcium-dependent S100B binding motif. This S100B binding motif is conserved in several other S100B target proteins, including the p53 protein. Cellular studies using a truncated ATAD3A mutant that is deficient for mitochondrial import revealed that S100B prevents cytoplasmic ATAD3A mutant aggregation and restored its mitochondrial localization. With these results in mind, we propose that S100B could assist the newly synthesized ATAD3A protein, which harbors the consensus S100B binding domain for proper folding and subcellular localization. Such a function for S100B might also help to explain the rescue of nuclear translocation and activation of the temperature-sensitive p53val135 mutant by S100B at nonpermissive temperatures.

DOI10.1128/MCB.01468-09
Alternate JournalMol. Cell. Biol.
PubMed ID20351179
PubMed Central IDPMC2876520
Grant ListCA107745 / CA / NCI NIH HHS / United States
GM58888 / GM / NIGMS NIH HHS / United States