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In the intracellular pathogen <jats:italic>Brucella\u00a0suis<\/jats:italic>, a type <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> secretion system mediates the translocation of virulence factors into host cells and it is essential for pathogenicity. VirB8 is a core component of the secretion system and dimerization is important for functionality of the protein complex. We set out to study dimerization and possible conformational changes of VirB8 from <jats:italic>B.\u00a0suis<\/jats:italic> (VirB8s) using nuclear magnetic resonance, X\u2010ray crystallography, and differential scanning fluorimetry. We identified changes of the protein induced by a concentration\u2010dependent monomer\u2010to\u2010dimer transition of the periplasmic domain (VirB8sp). We also show that the presence of the detergent <jats:styled-content style=\"fixed-case\">CHAPS<\/jats:styled-content> alters several signals in the heteronuclear single quantum coherence (<jats:styled-content style=\"fixed-case\">HSQC<\/jats:styled-content>) spectra and some of these chemical shift changes correspond to those observed during monomer\u2013dimer transition. X\u2010ray analysis of a monomeric variant (VirB8sp<jats:sup>M102R<\/jats:sup>) demonstrates that significant structural changes occur in the protein's \u03b1\u2010helical regions (\u03b12 and \u03b14). We localized chemical shift changes of residues at the dimer interface as well as to the \u03b11 helix that links this interface to a surface groove that binds dimerization inhibitors. Fragment\u2010based screening identified small molecules that bind to VirB8sp and two of them have differential binding affinity for wild\u2010type and the VirB8sp<jats:sup>M102R<\/jats:sup> variant underlining their different conformations. The observed chemical shift changes suggest conformational changes of VirB8s during monomer\u2013dimer transition that may play a role during secretion system assembly or function and they provide insights into the mechanism of inhibitor action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Database<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BMRB<\/jats:styled-content> accession no. 26852 and PDB <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.rcsb.org\/pdb\/search\/structidSearch.do?structureId=5JBS\">5JBS<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.14049","type":"journal-article","created":{"date-parts":[[2017,2,25]],"date-time":"2017-02-25T20:52:43Z","timestamp":1488055963000},"page":"1218-1232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Monomer\u2010to\u2010dimer transition of <i>Brucella\u00a0suis<\/i> type <scp>IV<\/scp> 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