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Insights into pneumococcal fratricide from the crystal structures of the modular killing factor LytC
Authors
José Luis García
Pedro García
+9 more
Ana González
Juan A. Hermoso
Martín Martínez-Ripoll
Shahriar Mobashery
María Morales
Inmaculada Pérez-Dorado
Reyes Sanles
Waldemar Striker
Waldemar Vollmer
Publication date
31 August 2021
Publisher
'Springer Science and Business Media LLC'
Doi
Cite
Abstract
7 pags, 3 figs, 1 tabThe first structure of a pneumococcal autolysin, that of the LytC lysozyme, has been solved in ternary complex with choline and a pneumococcal peptidoglycan (PG) fragment. The active site of the hydrolase module is not fully exposed but is oriented toward the choline-binding module, which accounts for its unique in vivo features in PG hydrolysis, its activation and its regulatory mechanisms. Because of the unusual hook-shaped conformation of the multimodular protein, it is only able to hydrolyze non-cross-linked PG chains, an assertion validated by additional experiments. These results explain the activation of LytC by choline-binding protein D (CbpD) in fratricide, a competence-programmed mechanism of predation of noncompetent sister cells. The results provide the first structural insights to our knowledge into the critical and central function that LytC plays in pneumococcal virulence and explain a long-standing puzzle of how murein hydrolases can be controlled to avoid self-lysis during bacterial growth and division. © 2010 Nature America, Inc. All rights reserved.This work was supported by grants from the Spanish Ministry of Science and Technology (BFU2008-01711, SAF2006-00390), EU-CP223111 (CAREPNEUMO, European Union), the COMBACT program (S-BIO-0260/2006) and CIBER de Enfermedades Respiratorias (CIBERES). CIBERES is an initiative of Instituto de Salud Carlos III. The work in the US was supported by the US National Institutes of Health. W.V. was supported by the European Commission (EUR-INTAFAR project). I.P.-D. was a fellow of the Consejo Superior de Investigaciones Científicas
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Last time updated on 14/11/2021