eprintid: 24029
rev_number: 30
userid: 4439
dir: disk0/00/02/40/29
datestamp: 2015-05-12 17:52:06
lastmod: 2021-06-13 01:55:19
status_changed: 2015-05-12 17:52:06
type: article
metadata_visibility: show
contact_email: bahar@pitt.edu
item_issues_id: similar_title_28516
item_issues_id: duplicate_title_28516
item_issues_type: similar_title
item_issues_type: duplicate_title
item_issues_description: Similar title to 


    <span class="person_name">Cheng, Mary Hongying</span> and <span class="person_name">Bahar, Ivet</span>
  

(2014)

<a href="http://d-scholarship.pitt.edu/cgi/users/home?screen=EPrint::View&amp;eprintid=28516"><xhtml:em xmlns:xhtml="http://www.w3.org/1999/xhtml">Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle.</xhtml:em></a>


    PLoS Computational Biology, 10 (10).
     e1003879.
     ISSN 1553-7358
item_issues_description: Duplicate title to 


    <span class="person_name">Cheng, Mary Hongying</span> and <span class="person_name">Bahar, Ivet</span>
  

(2014)

<a href="http://d-scholarship.pitt.edu/cgi/users/home?screen=EPrint::View&amp;eprintid=28516"><xhtml:em xmlns:xhtml="http://www.w3.org/1999/xhtml">Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle.</xhtml:em></a>


    PLoS Computational Biology, 10 (10).
     e1003879.
     ISSN 1553-7358
item_issues_timestamp: 2016-07-02 06:15:49
item_issues_timestamp: 2017-08-25 06:02:13
item_issues_status: autoresolved
item_issues_status: autoresolved
item_issues_count: 0
eprint_status: archive
creators_name: Cheng, MH
creators_name: Bahar, I
creators_email: 
creators_email: bahar@pitt.edu
creators_id: 
creators_id: BAHAR
contributors_type: http://www.loc.gov/loc.terms/relators/EDT
contributors_name: de Groot, Bert L.
title: Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle
ispublished: pub
divisions: sch_med_Computational_Systems_Biology
full_text_status: public
abstract: Neurotransmitter: sodium symporters (NSSs) regulate neuronal signal transmission by clearing excess neurotransmitters from the synapse, assisted by the co-transport of sodium ions. Extensive structural data have been collected in recent years for several members of the NSS family, which opened the way to structure-based studies for a mechanistic understanding of substrate transport. Leucine transporter (LeuT), a bacterial orthologue, has been broadly adopted as a prototype in these studies. This goal has been elusive, however, due to the complex interplay of global and local events as well as missing structural data on LeuT N-terminal segment. We provide here for the first time a comprehensive description of the molecular events leading to substrate/Na+ release to the postsynaptic cell, including the structure and dynamics of the N-terminal segment using a combination of molecular simulations. Substrate and Na+-release follows an influx of water molecules into the substrate/Na+-binding pocket accompanied by concerted rearrangements of transmembrane helices. A redistribution of salt bridges and cation-π interactions at the N-terminal segment prompts substrate release. Significantly, substrate release is followed by the closure of the intracellular gate and a global reconfiguration back to outward-facing state to resume the transport cycle. Two minimally hydrated intermediates, not structurally resolved to date, are identified: one, substrate-bound, stabilized during the passage from outward- to inward-facing state (holo-occluded), and another, substrate-free, along the reverse transition (apo-occluded).
date: 2014-01-01
date_type: published
publication: PLoS Computational Biology
volume: 10
number: 10
refereed: TRUE
issn: 1553-734X
id_number: 10.1371/journal.pcbi.1003879
other_id: NLM PMC4191883
pmcid: PMC4191883
pmid: 25299050
citation:   Cheng, MH and Bahar, I  (2014) Complete Mapping of Substrate Translocation Highlights the Role of LeuT N-terminal Segment in Regulating Transport Cycle.  PLoS Computational Biology, 10 (10).   ISSN 1553-734X     
document_url: http://d-scholarship-dev.library.pitt.edu/24029/1/journal.pcbi.1003879.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/24029/4/licence.txt