Structure and assembly of an augmented Sm-like archaeal protein 14-mer

  1. Cameron Mura*,
  2. Martin Phillips,
  3. Anna Kozhukhovsky*, and
  4. David Eisenberg*,,
  1. *Howard Hughes Medical Institute, Molecular Biology Institute, and Department of Energy Institute for Genomics and Proteomics, 201 Boyer Hall/ Molecular Biology Institute, University of California, Box 951570, Los Angeles, CA 90095-1570; and Departments of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, CA 90095
  1. Contributed by David Eisenberg

Abstract

To better understand the roles of Sm proteins in forming the cores of many RNA-processing ribonucleoproteins, we determined the crystal structure of an atypical Sm-like archaeal protein (SmAP3) in which the conserved Sm domain is augmented by a previously uncharacterized, mixed α/β C-terminal domain. The structure reveals an unexpected SmAP3 14-mer that is perforated by a cylindrical pore and is bound to 14 cadmium (Cd2+) ions. Individual heptamers adopt either “apical” or “equatorial” conformations that chelate Cd2+ differently. SmAP3 forms supraheptameric oligomers (SmAP3)n = 7,14,28 in solution, and assembly of the asymmetric 14-mer is modulated by differential divalent cation-binding in apical and equatorial subunits. Phylogenetic and sequence analyses substantiate SmAP3s as a unique subset of SmAPs. These results distinguish SmAP3s from other Sm proteins and provide a model for the structure and properties of Sm proteins >100 residues in length, e.g., several human Sm proteins.

Footnotes

  • To whom correspondence should be addressed. E-mail: david{at}mbi.ucla.edu.

  • Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code ).

  • Abbreviations:
    1. RNP, ribonucleoprotein

    2. snRNP, small nuclear RNP

    3. SmAP, Sm-like archaeal protein

    4. NCS, noncrystallographic symmetry

    5. a.u., asymmetric unit

    6. MAD, multiwavelength anomalous dispersion

    7. rmsd, rms deviation

    8. Afu, Archaeoglobus fulgidus

    9. Pae, Pyrobaculum aerophilum

    10. Mth, Methanobacterium thermautotrophicum

    11. CTD, C-terminal domain

    12. ssRNA, single-stranded RNA

    13. UMP, uridine-5′-monophosphate

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