Structural conservation of neurotropism-associated VspA within the variable Borrelia Vsp-OspC lipoprotein family

Wolfram R. Zückert, Tatiana A. Kerentseva, Catherine L. Lawson, Alan G. Barbour

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to avoid the immune response. One of these proteins, VspA of Borrelia turicatae, is also associated with neurotropism in infected mice. Vsp proteins are highly polymorphic in sequence, which may relate to their specific antibody reactivities and host cell interactions. To determine whether sequence variations affect protein structure, we compared B. turicatae VspA with three related proteins: VspB of B. turicatae, Vsp26 of the relapsing fever agent Borrelia hermsii, and OspC of the Lyme disease spirochete Borrelia burgdorferi. Recombinant non-lipidated proteins were purified by affinity or ion exchange chromatography. Circular dichroism spectra revealed similar, highly α-helical secondary structures for all four proteins. In vitro assays demonstrated protease-resistant, thermostable Vsp cores starting at a conserved serine at position 34 (Ser34). All proteins aggregate as dimers in solution. In situ trypsin treatment and surface protein cross-linking showed that the native lipoproteins also form protease-resistant dimers. These findings indicate that Vsp proteins have a common compact fold and that their established functions are based on localized polymorphisms. Two forms of VspA crystals suitable for structure determination by x-ray diffraction methods have been obtained.

Original languageEnglish (US)
Pages (from-to)457-463
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number1
DOIs
StatePublished - Jan 5 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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