Structure of a delivery protein for an AAA+ protease in complex with a peptide degradation tag

Mol Cell. 2003 Aug;12(2):365-72. doi: 10.1016/j.molcel.2003.08.014.

Abstract

Substrate selection by AAA+ ATPases that function to unfold proteins or alter protein conformation is often regulated by delivery or adaptor proteins. SspB is a protein dimer that binds to the ssrA degradation tag and delivers proteins bearing this tag to ClpXP, an AAA+ protease, for degradation. Here, we describe the structure of the peptide binding domain of H. influenzae SspB in complex with an ssrA peptide at 1.6 A resolution. The ssrA peptides are bound in well-defined clefts located at the extreme ends of the SspB homodimer. SspB contacts residues within the N-terminal and central regions of the 11 residue ssrA tag but leaves the C-terminal residues exposed and positioned to dock with ClpX. This structure, taken together with biochemical analysis of SspB, suggests mechanisms by which proteins like SspB escort substrates to AAA+ ATPases and enhance the specificity and affinity of target recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Crystallography, X-Ray
  • Dimerization
  • Endopeptidase Clp
  • Haemophilus influenzae / enzymology
  • Models, Biological
  • Models, Molecular
  • Multigene Family
  • Peptides / chemistry*
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Bacterial / chemistry
  • Serine Endopeptidases / chemistry*

Substances

  • Peptides
  • RNA, Bacterial
  • tmRNA
  • Serine Endopeptidases
  • Endopeptidase Clp
  • Adenosine Triphosphatases

Associated data

  • PDB/1OU8
  • PDB/1OU9
  • PDB/1OUL