Nanobody-aided structure determination of the EpsI:EpsJ pseudopilin heterodimer from Vibrio vulnificus

J Struct Biol. 2009 Apr;166(1):8-15. doi: 10.1016/j.jsb.2008.11.008. Epub 2008 Dec 10.

Abstract

Pseudopilins form the central pseudopilus of the sophisticated bacterial type 2 secretion systems. The crystallization of the EpsI:EpsJ pseudopilin heterodimer from Vibrio vulnificus was greatly accelerated by the use of nanobodies, which are the smallest antigen-binding fragments derived from heavy-chain only camelid antibodies. Seven anti-EpsI:EpsJ nanobodies were generated and co-crystallization of EpsI:EpsJ nanobody complexes yielded several crystal forms very rapidly. In the structure solved, the nanobodies are arranged in planes throughout the crystal lattice, linking layers of EpsI:EpsJ heterodimers. The EpsI:EpsJ dimer observed confirms a right-handed architecture of the pseudopilus, but, compared to a previous structure of the EpsI:EpsJ heterodimer, EpsI differs 6 degrees in orientation with respect to EpsJ; one loop of EpsJ is shifted by approximately 5A due to interactions with the nanobody; and a second loop of EpsJ underwent a major change of 17A without contacts with the nanobody. Clearly, nanobodies accelerate dramatically the crystallization of recalcitrant protein complexes and can reveal conformational flexibility not observed before.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antigen-Antibody Complex / chemistry
  • Binding Sites, Antibody
  • Camelids, New World / immunology
  • Complementarity Determining Regions / chemistry
  • Crystallization / methods
  • Crystallography, X-Ray
  • Epitopes / chemistry
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / immunology
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Vibrio vulnificus / chemistry*

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Complementarity Determining Regions
  • Epitopes
  • Immunoglobulin Heavy Chains
  • Membrane Transport Proteins
  • Recombinant Proteins

Associated data

  • PDB/3CFI