The mammalian DUF59 protein Fam96a forms two distinct types of domain-swapped dimer
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Fam96a mRNA, which encodes a mammalian DUF59 protein, is enriched in macrophages. Recombinant human Fam96a forms stable monomers and dimers in solution. Crystal structures of these two forms revealed that each adopts a distinct type of domain-swapped dimer, one of which is stabilized by zinc binding. Two hinge loops control Fam96a domain swapping; both are flexible and highly conserved, suggesting that domain swapping may be a common feature of eukaryotic but not bacterial DUF59 proteins. The derived monomer fold of Fam96a diverges from that of bacterial DUF59 counterparts in that the C-terminal region of Fam96a is much longer and is positioned on the opposite side of the N-terminal core fold. The putative metal-binding site of bacterial DUF59 proteins is not conserved in Fam96a, but Fam96a interacts tightly in vitro with Ciao1, the cytosolic iron-assembly protein. Moreover, Fam96a and Ciao1 can be co-immunoprecipitated, suggesting that the interaction also occurs in vivo. Although predicted to have a signal peptide, it is shown that Fam96a is cytoplasmic. The data reveal that eukaryotic DUF59 proteins share intriguing characteristics with amyloidogenic proteins.
Acta Crystallographica Section D: Biological Crystallography
© 2012 International Union of Crystallography. This is the Authorised Electronic Reprint version of the following article: The mammalian DUF59 protein Fam96a forms two distinct types of domain-swapped dimer, Acta Crystallographica Section D, 68(6),637–648,2012, which has been published in final form at DOI:10.1107/S0907444912006592
Medicinal and Biomolecular Chemistry not elsewhere classified