Solution NMR structure and X-ray absorption analysis of the C-terminal zinc-binding domain of the SecA ATPase

Biochemistry. 2004 Jul 27;43(29):9361-71. doi: 10.1021/bi0493057.

Abstract

The solution NMR structure of a 22-residue Zn(2+)-binding domain (ZBD) from Esherichia coli preprotein translocase subunit SecA is presented. In conjunction with X-ray absorption analysis, the NMR structure shows that three cysteines and a histidine in the sequence CXCXSGX(8)CH assume a tetrahedral arrangement around the Zn(2+) atom, with an average Zn(2+)-S bond distance of 2.30 A and a Zn(2+)-N bond distance of 2.03 A. The NMR structure shows that ND1 of His20 binds to the Zn(2+) atom. The ND1-Zn(2+) bond is somewhat strained: it makes an angle of approximately 17 degrees with the plane of the ring, and it also shows a significant "in-plane" distortion of 13 degrees. A comprehensive sequence alignment of the SecA-ZBD from many different organisms shows that, along with the four Zn(2+) ligands, there is a serine residue (Ser12) that is completely conserved. The NMR structure indicates that the side chain of this serine residue forms a strong hydrogen bond with the thiolate of the third cysteine residue (Cys19); therefore, the conserved serine appears to have a critical role in the structure. SecB, an export-specific chaperone, is the only known binding partner for the SecA-ZBD. A phylogenetic analysis using 86 microbial genomes shows that 59 of the organisms carry SecA with a ZBD, but only 31 of these organisms also possess a gene for SecB, indicating that there may be uncharacterized binding partners for the SecA-ZBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Electron Probe Microanalysis
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Phylogeny
  • Protein Conformation
  • SEC Translocation Channels
  • SecA Proteins
  • Sequence Homology, Amino Acid
  • Zinc / metabolism*

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • SEC Translocation Channels
  • Adenosine Triphosphatases
  • SecA Proteins
  • Zinc