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The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation

Kadaba, Neena S. and Kaiser, Jens T. and Johnson, Eric and Lee, Allen and Rees, Douglas C. (2008) The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation. Science, 321 (5886). pp. 250-253. ISSN 0036-8075. PMCID PMC2527972. doi:10.1126/science.1157987. https://resolver.caltech.edu/CaltechAUTHORS:20141118-161003885

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Abstract

The crystal structure of the high-affinity Escherichia coli MetNI methionine uptake transporter, a member of the adenosine triphosphate (ATP)–binding cassette (ABC) family, has been solved to 3.7 angstrom resolution. The overall architecture of MetNI reveals two copies of the adenosine triphosphatase (ATPase) MetN in complex with two copies of the transmembrane domain MetI, with the transporter adopting an inward-facing conformation exhibiting widely separated nucleotide binding domains. Each MetI subunit is organized around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK) ABC transporters. In addition to the conserved nucleotide binding domain of the ABC family, MetN contains a carboxyl-terminal extension with a ferredoxin-like fold previously assigned to a conserved family of regulatory ligand-binding domains. These domains separate the nucleotide binding domains and would interfere with their association required for ATP binding and hydrolysis. Methionine binds to the dimerized carboxyl-terminal domain and is shown to inhibit ATPase activity. These observations are consistent with an allosteric regulatory mechanism operating at the level of transport activity, where increased intracellular levels of the transported ligand stabilize an inward-facing, ATPase-inactive state of MetNI to inhibit further ligand translocation into the cell.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1157987 DOIArticle
http://www.sciencemag.org/content/321/5886/250PublisherArticle
http://www.sciencemag.org/content/321/5886/250/suppl/DC1PublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527972/PubMed CentralArticle
ORCID:
AuthorORCID
Kaiser, Jens T.0000-0002-5948-5212
Rees, Douglas C.0000-0003-4073-1185
Additional Information:© 2008 American Association for the Advancement of Science. 18 March 2008; Accepted 10 June 2008. We thank H. Pinkett, Z. Liu, O. Lewinson, L. Thompson, D. Tirrell, and J. B. Howard for helpful discussions and the staffs of the Stanford Synchrotron Radiation Laboratory (SSRL) and the Advanced Light Source (ALS) for their assistance during crystal screening and data collection. This work was supported in part by NIH grant GM45162. We would like to acknowledge the Gordon and Betty Moore Foundation for support of the Molecular Observatory at Caltech. Operations at SSRL and ALS are supported by the U.S. Department of Energy and NIH. Coordinates and structure factors for MetNI and the MetN-C2 domain have been deposited in the Protein Data Bank (www.rcsb.org/pdb) (38) with the identification numbers 3DHW and 3DHX, respectively.
Funders:
Funding AgencyGrant Number
NIHGM45162
Gordon and Betty Moore FoundationUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
Issue or Number:5886
PubMed Central ID:PMC2527972
DOI:10.1126/science.1157987
Record Number:CaltechAUTHORS:20141118-161003885
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141118-161003885
Official Citation:Kadaba, N. S., Kaiser, J. T., Johnson, E., Lee, A., & Rees, D. C. (2008). The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation. Science, 321(5886), 250-253. doi: 10.1126/science.1157987
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51927
Collection:CaltechAUTHORS
Deposited By: Joanne McCole
Deposited On:19 Nov 2014 21:46
Last Modified:10 Nov 2021 19:17

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