期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 10, 页码 4882-4893出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.671172
关键词
bacteriophage; enzyme catalysis; mass spectrometry (MS); oligomerization; protein structure; Clostridia; antimicrobial; endolysin; native mass spectrometry; secondary translation
资金
- Spanish Ministry of Economy and Competitiveness Project [RTA 2011-00024-C02-01]
- Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria grant
- Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant [BB/J004529/1]
- Leibniz Association Grant [SAW-2014-HPI-4]
- EU FP7 e-Infrastructures Program, Grant WeNMR [261572]
- BBSRC [BBS/E/F/00044453] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/F/00044453] Funding Source: researchfish
Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C-terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full-length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections.
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