The Legionella collagen-like protein employs a distinct binding mechanism for the recognition of host glycosaminoglycans

Saima Rehman, Anna Katarina Antonovic, Ian E. McIntire, Huaixin Zheng, Leanne Cleaver, Maria Baczynska, Carlton O. Adams, Theo Portlock, Katherine Richardson, Rosie Shaw, Alain Oregioni, Giulia Mastroianni, Sara B.M. Whittaker, Geoff Kelly, Christian D. Lorenz, Arianna Fornili*, Nicholas P. Cianciotto*, James A. Garnett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number4912
JournalNat Commun
Volume15
Issue number1
Early online date8 Jun 2024
DOIs
Publication statusE-pub ahead of print - 8 Jun 2024

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