title: Structure and molecular evolution of CDGSH iron-sulfur domains.
abstract: The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs.
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Lin
authors.forename: Liman
authors.initials: L
authors.lastname: Zhang
authors.forename: Shaomei
authors.initials: S
authors.lastname: Lai
authors.forename: Keqiong
authors.initials: K
authors.lastname: Ye
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000235:genetics*; D042201:Magnetospirillum / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D041543:Pyrobaculum / Q000378:metabolism; D043367:Ralstonia / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D007506:Iron-Sulfur Proteins