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Important mechanism for complement evasion is acquisition of the main host complement inhibitor, factor H (FH). By determining the 2.2 \u00c5 crystal structure of Factor H binding protein A (FhbA) from<jats:italic>Borrelia hermsii<\/jats:italic>in complex with FH domains 19\u201320, combined with extensive mutagenesis, we identified the structural mechanism by which<jats:italic>B<\/jats:italic>.<jats:italic>hermsii<\/jats:italic>utilizes FhbA in immune evasion. Moreover, structure-guided sequence database analysis identified a new family of FhbA-related immune evasion molecules from Lyme disease and relapsing fever<jats:italic>Borrelia<\/jats:italic>. Conserved FH-binding mechanism within the FhbA-family was verified by analysis of a novel FH-binding protein from<jats:italic>B<\/jats:italic>.<jats:italic>duttonii<\/jats:italic>. By sequence analysis, we were able to group FH-binding proteins of<jats:italic>Borrelia<\/jats:italic>into four distinct phyletic types and identified novel putative FH-binding proteins. The conserved FH-binding mechanism of the FhbA-related proteins could aid in developing new approaches to inhibit virulence and complement resistance in<jats:italic>Borrelia<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010338","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T17:39:48Z","timestamp":1647625188000},"page":"e1010338","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanism of Borrelia immune evasion by FhbA-related proteins"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-9391","authenticated-orcid":true,"given":"Konstantin","family":"Kogan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-625X","authenticated-orcid":true,"given":"Karita","family":"Haapasalo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommi","family":"Kotila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pekka","family":"Lappalainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0880-1067","authenticated-orcid":true,"given":"Taru","family":"Meri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ppat.1010338.ref001","volume-title":"Complement Immune Evasion by Spirochetes in Spirochete Biology: The Post Genomic Era.","author":"A.S. 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