7ZJJ

CspZ (BbCRASP-2) from Borrelia burgdorferi strain B379

7ZJJ の概要

• エントリーDOI: 10.2210/pdb7zjj/pdb
• 分子名称: CspZ, NITRATE ION (3 entities in total)
• 機能のキーワード: lyme disease, borreliosis, outer surface protein, bbh06, complement binding., membrane protein
• 由来する生物種: Borreliella burgdorferi (Lyme disease spirochete)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25535.13

構造登録者

Brangulis, K.,Marcinkiewicz, A.,Hart, T.M.,Dupuis, A.P.,Zamba Campero, M.,Nowak, T.A.,Stout, J.L.,Akopjana, I.,Kazaks, A.,Bogans, J.,Ciota, A.T.,Kraiczy, P.,Kolokotronis, S.O.,Lin, Y.-P. (登録日: 2022-04-11, 公開日: 2023-04-19, 最終更新日: 2024-02-07)

主引用文献

Marcinkiewicz, A.L.,Brangulis, K.,Dupuis 2nd, A.P.,Hart, T.M.,Zamba-Campero, M.,Nowak, T.A.,Stout, J.L.,Akopjana, I.,Kazaks, A.,Bogans, J.,Ciota, A.T.,Kraiczy, P.,Kolokotronis, S.O.,Lin, Y.P.
Structural evolution of an immune evasion determinant shapes pathogen host tropism.
Proc.Natl.Acad.Sci.USA, 120:e2301549120-e2301549120, 2023

PubMed Abstract: Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease-causing bacterium () is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick-transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement-mediated immune clearance, produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH-binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host-specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, and identifying minor variation localized in the FH-binding interface yielding bird and rodent FH-specific binding activity that impacts infectivity. Swapping the divergent region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. We further linked these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism.

PubMed: 37364114
DOI: 10.1073/pnas.2301549120

実験手法

X-RAY DIFFRACTION (2.1 Å)