Transport Mechanism of a Bacterial Homologue of Glutamate Transporters

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Nature

DOI:https://doi.org/10.1038/nature08616· OSTI ID:1019619

Reyes, N; Ginter, C; Boudker, O

Glutamate transporters are integral membrane proteins that catalyse a thermodynamically uphill uptake of the neurotransmitter glutamate from the synaptic cleft into the cytoplasm of glia and neuronal cells by harnessing the energy of pre-existing electrochemical gradients of ions. Crucial to the reaction is the conformational transition of the transporters between outward and inward facing states, in which the substrate binding sites are accessible from the extracellular space and the cytoplasm, respectively. Here we describe the crystal structure of a double cysteine mutant of a glutamate transporter homologue from Pyrococcus horikoshii, GltPh, which is trapped in the inward facing state by cysteine crosslinking. Together with the previously determined crystal structures of Glt{sub Ph} in the outward facing state, the structure of the crosslinked mutant allows us to propose a molecular mechanism by which Glt{sub Ph} and, by analogy, mammalian glutamate transporters mediate sodium-coupled substrate uptake.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019619
• Report Number(s): BNL--95464-2011-JA
• Journal Information: Nature, Journal Name: Nature Journal Issue: 7275 Vol. 462; ISSN 0028-0836
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
CRYSTAL STRUCTURE
CYSTEINE
CYTOPLASM
EXTRACELLULAR SPACE
MEMBRANE PROTEINS
MUTANTS
SUBSTRATES
TRANSPORT
national synchrotron light source