TY - JOUR
T1 - Structural analysis of the outer surface proteins from Borrelia burgdorferi paralogous gene family 54 that are thought to be the key players in the pathogenesis of Lyme disease
AU - Brangulis, Kalvis
AU - Akopjana, Ināra
AU - Petrovskis, Ivars
AU - Kazaks, Andris
AU - Tars, Kaspars
N1 - Funding Information:
This work was supported by the S. Weiss and Christian Feiler during the experiment. Diffraction data for B. burgdorferi BBA65 was collected at the MAX-lab beamline I911-3 (Lund, Sweden), and we acknowledge the staff at MAX-lab synchrotron for their support during the data collection. ERDF grant Nr. 1.1.1.2/VIAA/1/16/144 to K.B. Diffraction data for B. spielmanii BSA64 have been collected on BL14.1 at the BESSY II electron storage ring operated by the Helmholtz-Zentrum Berlin. We would particularly like to acknowledge the help and support of Manfred
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. Through a complex enzootic cycle, the bacteria transfer between two different hosts: Ixodes ticks and mammalian organisms. At the start of the tick blood meal, the spirochetes located in the tick gut upregulate the expression of several genes, mainly coding for outer surface proteins. Outer surface proteins belonging to the paralogous gene family 54 (PFam54) have been shown to be the most upregulated among the other borrelial proteins and the results clearly point to the potential importance of these proteins in the pathogenesis of Lyme disease. The significance of PFam54 proteins is confirmed by the fact that of all ten PFam54 proteins, BBA64 and BBA66 are necessary for the transfer of B. burgdorferi from infected Ixodes ticks to mammalian hosts. To enhance the understanding of the pathogenesis of Lyme disease and to promote the development of novel therapies against Lyme disease, we solved the crystal structure of the PFam54 member BBA65. Additionally, we report the structure of the B. burgdorferi BBA64 orthologous protein from B. spielmanii. Together with the previously determined crystal structures of five PFam54 members and several related proteins, we performed a comprehensive structural analysis for this important group of proteins. In addition to revealing the molecular aspects of the proteins, the structural data analysis suggests that the gene families PFam54 and PFam60, which have long been referred to as separate paralogous families, should be merged into one and designated as PFam54_60.
AB - Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. Through a complex enzootic cycle, the bacteria transfer between two different hosts: Ixodes ticks and mammalian organisms. At the start of the tick blood meal, the spirochetes located in the tick gut upregulate the expression of several genes, mainly coding for outer surface proteins. Outer surface proteins belonging to the paralogous gene family 54 (PFam54) have been shown to be the most upregulated among the other borrelial proteins and the results clearly point to the potential importance of these proteins in the pathogenesis of Lyme disease. The significance of PFam54 proteins is confirmed by the fact that of all ten PFam54 proteins, BBA64 and BBA66 are necessary for the transfer of B. burgdorferi from infected Ixodes ticks to mammalian hosts. To enhance the understanding of the pathogenesis of Lyme disease and to promote the development of novel therapies against Lyme disease, we solved the crystal structure of the PFam54 member BBA65. Additionally, we report the structure of the B. burgdorferi BBA64 orthologous protein from B. spielmanii. Together with the previously determined crystal structures of five PFam54 members and several related proteins, we performed a comprehensive structural analysis for this important group of proteins. In addition to revealing the molecular aspects of the proteins, the structural data analysis suggests that the gene families PFam54 and PFam60, which have long been referred to as separate paralogous families, should be merged into one and designated as PFam54_60.
KW - Ixodes ticks
KW - Lyme borreliosis
KW - Paralogous proteins
KW - Spirochetes
KW - X-ray crystallography
UR - http://www.scopus.com/inward/record.url?scp=85080972089&partnerID=8YFLogxK
U2 - 10.1016/j.jsb.2020.107490
DO - 10.1016/j.jsb.2020.107490
M3 - Article
C2 - 32135236
AN - SCOPUS:85080972089
SN - 1047-8477
VL - 210
SP - 107490
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 2
M1 - 107490
ER -