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Title: Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [2];  [1]; ORCiD logo [2]
  1. California Institute of Technology (CalTech), Pasadena, CA (United States). Division of Chemistry and Chemical Engineering
  2. California Institute of Technology (CalTech), Pasadena, CA (United States). Division of Chemistry and Chemical Engineering and Howard Hughes Medical Inst.

The Escherichia coli methionine ABC transporter MetNI exhibits both high-affinity transport toward L-methionine and broad specificity toward methionine derivatives, including D-methionine. In this work, we characterize the transport of D-methionine derivatives by the MetNI transporter. Unexpectedly, the N229A substrate-binding deficient variant of the cognate binding protein MetQ was found to support high MetNI transport activity toward D-selenomethionine. We determined the crystal structure at 2.95 Å resolution of the ATPγS-bound MetNIQ complex in the outward-facing conformation with the N229A apo MetQ variant. This structure revealed conformational changes in MetQ providing substrate access through the binding protein to the transmembrane translocation pathway. MetQ likely mediates uptake of methionine derivatives through two mechanisms: in the methionine-bound form delivering substrate from the periplasm to the transporter (the canonical mechanism) and in the apo form by facilitating ligand binding when complexed to the transporter (the noncanonical mechanism). This dual role for substrate-binding proteins is proposed to provide a kinetic strategy for ABC transporters to transport both high- and low-affinity substrates present in a physiological concentration range.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); Vietnam Ministry of Education and Training; Gordon and Betty Moore Foundation; Beckman Institute; National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); National Center for Research Resources (NCRR)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1625025
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, Issue 45; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 24 works
Citation information provided by
Web of Science

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Cited By (3)

Structures of the Neisseria meningitides methionine‐binding protein MetQ in substrate‐free form and bound to l ‐ and d ‐methionine isomers journal August 2019
Profiling the Escherichia coli membrane protein interactome captured in Peptidisc libraries journal July 2019
Development of specific l -methionine sensors by FRET-based protein engineering journal January 2019