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Structural studies of a bacterial siderophore ABC importer YbtPQ


EMSL Project ID
51081

Abstract

Iron (Fe) is an essential element for not only the well-being of hosts, but also the growth and virulence of microbes(Begg, 2019). One of the major Fe uptake processes in bacteria is through siderophores, a group of small molecules with extremely high affinity to Fe that are synthesized and secreted by the microbes. The metal-chelated siderophores are then imported by the ATP-binding cassette (ABC) importers. Despite the intensive studies on many ABC transporters in the literature, the detailed molecular mechanism of how metal-chelated siderophores are imported by the group of siderophore ABC importers, such as YbtPQ from uropathogenic Escherichia coli (UPEC) causing urinary tract infections (UTI), is entirely unknown. We have already determined the structure of YbtPQ by cryo-EM to ~3.7Å, which surprisingly adopts the folding of typical ABC exporters rather than known ABC importers. To better understand its mechanism, we intend to pursue the following aims:

Specific Aim #1: Investigate the substrate selectivity of YbtPQ using Ybt chelated with various metals.
Specific Aim #2: Define a complete transport cycle by structure determination of YbtPQ in other major physiological conformations.

The knowledge gained here is expected to fundamentally advance the field of siderophore uptake and have positive translational impact because, it will allow us to understand how microbes obtain necessary metal nutrients using siderophores. Such understanding could then be used to develop drugs to specifically target this process in human pathogens.

Project Details

Start Date
2019-10-15
End Date
2020-07-15
Status
Closed

Team

Principal Investigator

Hongjin Zheng
Institution
University of Colorado Anschutz Medical Campus

Team Members

David Farrell
Institution
University of Colorado Anschutz Medical Campus

Theo Humphreys
Institution
Oregon Health & Science University