TY - JOUR
T1 - The Legionella collagen-like protein employs a distinct binding mechanism for the recognition of host glycosaminoglycans
AU - Rehman, Saima
AU - Antonovic, Anna Katarina
AU - McIntire, Ian E.
AU - Zheng, Huaixin
AU - Cleaver, Leanne
AU - Baczynska, Maria
AU - Adams, Carlton O.
AU - Portlock, Theo
AU - Richardson, Katherine
AU - Shaw, Rosie
AU - Oregioni, Alain
AU - Mastroianni, Giulia
AU - Whittaker, Sara B.M.
AU - Kelly, Geoff
AU - Lorenz, Christian D.
AU - Fornili, Arianna
AU - Cianciotto, Nicholas P.
AU - Garnett, James A.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6/8
Y1 - 2024/6/8
N2 - Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires’ disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual trimer arrangement with a positively charged external surface and negatively charged solvent exposed internal cavity. Through molecular dynamics simulations, we show how the glycosaminoglycan chondroitin-4-sulphate associates with the Lcl-CTD surface via distinct binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate-binding mechanism.
AB - Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires’ disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual trimer arrangement with a positively charged external surface and negatively charged solvent exposed internal cavity. Through molecular dynamics simulations, we show how the glycosaminoglycan chondroitin-4-sulphate associates with the Lcl-CTD surface via distinct binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate-binding mechanism.
UR - http://www.scopus.com/inward/record.url?scp=85195533849&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-49255-4
DO - 10.1038/s41467-024-49255-4
M3 - Article
C2 - 38851738
AN - SCOPUS:85195533849
SN - 2041-1723
VL - 15
JO - Nat Commun
JF - Nat Commun
IS - 1
M1 - 4912
ER -