Structure to function of an α-glucan metabolic pathway that promotes Listeria monocytogenes pathogenesis.
Here we employ a 'systems structural biology' approach to functionally characterize an unconventional α-glucan metabolic pathway from the food-borne pathogen Listeria monocytogenes (Lm). Crystal structure determination coupled with basic biochemical and biophysical assays allowed for the identification of anabolic, transport, catabolic and regulatory portions of the cycloalternan pathway. These findings provide numerous insights into cycloalternan pathway function and reveal the mechanism of repressor, open reading frame, kinase (ROK) transcription regulators. Moreover, by developing a structural overview we were able to anticipate the cycloalternan pathway's role in the metabolism of partially hydrolysed starch derivatives and demonstrate its involvement in Lm pathogenesis. These findings suggest that the cycloalternan pathway plays a role in interspecies resource competition-potentially within the host gastrointestinal tract-and establish the methodological framework for characterizing bacterial systems of unknown function.
Center for Structural Genomics of Infectious Diseases and Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Samuel H
SH
Light
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Laty A
LA
Cahoon
Center for Structural Genomics of Infectious Diseases and Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Andrei S
AS
Halavaty
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Nancy E
NE
Freitag
Center for Structural Genomics of Infectious Diseases and Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Wayne F
WF
Anderson
D055592:Biophysical Phenomena; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D009844:Oligosaccharides / Q000378:metabolism*; D011487:Protein Conformation
D004798:Enzymes; D009844:Oligosaccharides; C488014:cycloalternan