| http://purl.uniprot.org/citations/35452090 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35452090 | http://www.w3.org/2000/01/rdf-schema#comment | "Integral membrane glutamate transporters couple the concentrative substrate transport to ion gradients. There is a wealth of structural and mechanistic information about this protein family. Recent studies of an archaeal homologue, GltPh, revealed transport rate heterogeneity, which is inconsistent with simple kinetic models; however, its structural and mechanistic determinants remain undefined. Here, we demonstrate that in a mutant GltPh, which exclusively populates the outward-facing state, at least two substates coexist in slow equilibrium, binding the substrate with different apparent affinities. Wild type GltPh shows similar binding properties, and modulation of the substate equilibrium correlates with transport rates. The low-affinity substate of the mutant is transient following substrate binding. Consistently, cryo-EM on samples frozen within seconds after substrate addition reveals the presence of structural classes with perturbed helical packing of the extracellular half of the transport domain in regions adjacent to the binding site. By contrast, an equilibrated structure does not show such classes. The structure at 2.2-Å resolution details a pattern of waters in the intracellular half of the domain and resolves classes with subtle differences in the substrate-binding site. We hypothesize that the rigid cytoplasmic half of the domain mediates substrate and ion recognition and coupling, whereas the extracellular labile half sets the affinity and dynamic properties."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.org/dc/terms/identifier | "doi:10.1085/jgp.202213131"xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/author | "Boudker O."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/author | "Reddy K.D."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/author | "Scopelliti A.J."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/author | "Ciftci D."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/name | "J Gen Physiol"xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/pages | "e202213131"xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/title | "The archaeal glutamate transporter homologue GltPh shows heterogeneous substrate binding."xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://purl.uniprot.org/core/volume | "154"xsd:string |
| http://purl.uniprot.org/citations/35452090 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35452090 |
| http://purl.uniprot.org/citations/35452090 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35452090 |
| http://purl.uniprot.org/uniprot/#_O59010-mappedCitation-35452090 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35452090 |
| http://purl.uniprot.org/uniprot/O59010 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/35452090 |