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Title: Structures and Mechanisms of a Novel Bacterial Transport System for Fatty Acids

Journal Article · · ChemBioChem: a European journal of chemical biology
 [1];  [2];  [2]; ORCiD logo [3]
  1. Department of Chemistry and Sarafan ChEM−H Institute Stanford University Stanford CA 94305 USA, Current address: School of Life Sciences The Chinese University of Hong Kong, Shatin New Territories Hong Kong China
  2. Department of Chemistry and Sarafan ChEM−H Institute Stanford University Stanford CA 94305 USA
  3. Department of Chemistry and Sarafan ChEM−H Institute Stanford University Stanford CA 94305 USA, Department of Microbiology and Immunology Stanford School of Medicine Stanford CA 94305 USA

Abstract Bacterial acquisition of metabolites is largely facilitated by transporters with unique substrate scopes. The tripartite ATP‐independent periplasmic (TRAP) transporters comprise a large family of bacterial proteins that facilitate the uptake of a variety of small molecules. It has been reported that some TRAP systems encode a fourth protein, the T component. The T‐component, or TatT, is predicted to be a periplasmic‐facing lipoprotein that enables the uptake of metabolites from the outer membrane. However, no substrates were revealed for any TatT and their functional role(s) remained enigmatic. We recently identified a homolog in Methylococcus capsulatus that binds to sterols, and herein, we report two additional homologs that demonstrate a preference for long‐chain fatty acids. Our bioinformatics, quantitative analyses of protein‐ligand interactions, and high‐resolution crystal structures suggest that TatTs might facilitate the trafficking of hydrophobic or lipophilic substrates and represent a new class of bacterial lipid and fatty acid transporters.

Sponsoring Organization:
USDOE
Grant/Contract Number:
NONE; AC02-76SF00515
OSTI ID:
1988324
Alternate ID(s):
OSTI ID: 1993344; OSTI ID: 1998183
Journal Information:
ChemBioChem: a European journal of chemical biology, Journal Name: ChemBioChem: a European journal of chemical biology Journal Issue: 15 Vol. 24; ISSN 1439-4227
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
France
Language:
English

References (42)

Lipid Transport Across Bacterial Membranes journal October 2022
Unique lipid composition of Treponema pallidum (Nichols virulent strain) journal June 1979
Microbial membrane lipid adaptations to high hydrostatic pressure in the marine environment journal January 2023
A Rapid Method of Total Lipid Extraction and Purification journal January 1959
The genetic requirements of fatty acid import by Mycobacterium tuberculosis within macrophages journal February 2019
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Structural and Thermodynamic Characterization of the Interaction between Two Periplasmic Treponema pallidum Lipoproteins that are Components of a TPR-Protein-Associated TRAP Transporter (TPAT) journal June 2012
Molecular analysis of the phoH gene, belonging to the phosphate regulon in Escherichia coli journal March 1993
Lipids of the Spirochaetales: Comparison of the Lipids of Several Members of the Genera Spirochaeta, Treponema, and Leptospira journal January 1974
Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis journal June 2017
De novo cholesterol biosynthesis in bacteria journal May 2023
A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin journal December 2022
EFI-EST, EFI-GNT, and EFI-CGFP: Enzyme Function Initiative (EFI) Web Resource for Genomic Enzymology Tools journal July 2023
Phaser crystallographic software journal July 2007
Structural, Bioinformatic, and In Vivo Analyses of Two Treponema pallidum Lipoproteins Reveal a Unique TRAP Transporter journal March 2012
The Spirochetes journal October 1977
The EFI Web Resource for Genomic Enzymology Tools: Leveraging Protein, Genome, and Metagenome Databases to Discover Novel Enzymes and Metabolic Pathways journal September 2019
Enhygromyxa salina gen. nov., sp. nov., a Slightly Halophilic Myxobacterium Isolated from the Coastal Areas of Japan journal January 2003
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks journal November 2003
The Lipid Handbook with CD-ROM book March 2007
Sialic acid transport inHaemophilus influenzaeis essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter journal October 2005
The IMG/M data management and analysis system v.7: content updates and new features journal November 2022
W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis journal April 2016
Highly accurate protein structure prediction with AlphaFold journal July 2021
Fatty acid transport by the lipophilic bacterium Nocardia asteroides journal May 1976
Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea journal January 2011
Transport of long-chain fatty acids by Escherichia coli: mapping and characterization of mutants in the fadL gene. journal July 1978
Lipids in sea water journal April 1966
Principles of Membrane Adaptation Revealed through Environmentally Induced Bacterial Lipidome Remodeling journal September 2020
Experimental Strategies for Functional Annotation and Metabolism Discovery: Targeted Screening of Solute Binding Proteins and Unbiased Panning of Metabolomes journal January 2015
Adaptation of the membrane lipids of a deep-sea bacterium to changes in hydrostatic pressure journal May 1985
Coot model-building tools for molecular graphics journal November 2004
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
CASTp 3.0: computed atlas of surface topography of proteins journal June 2018
Disruption of the Saccharomyces cerevisiae Homologue to the Murine Fatty Acid Transport Protein Impairs Uptake and Growth on Long-chain Fatty Acids journal March 1997
XDS journal January 2010
Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter journal August 2022
Organism-wide, cell-type-specific secretome mapping of exercise training in mice journal July 2023
The tripartite ATP-independent periplasmic (TRAP) transporters of bacteria and archaea journal August 2001
XCMS:  Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification journal February 2006
SAR11 lipid renovation in response to phosphate starvation journal June 2015
Lipid storage compounds in marine bacteria journal February 1997