A reentrant loop domain in the glutamate carrier EAAT1 participates in substrate binding and translocation.

Abstract:

:To investigate the structural determinants underlying transport by the glutamate transporter EAAT1, we mutated each of 24 highly conserved residues (P392 to Q415) to cysteine. A majority of these substituted cysteines react with the sulfhydryl-modifying reagent MTSEA, suggesting that they reside in an aqueous environment. The impermeant reagents MTSES and MTSET react with residues at each end of the domain (A395C and A414C), supporting a model that places these residues near the extracellular surface. Substrates and inhibitors block the reaction between MTS derivatives and A395C, and the cosubstrate, sodium, slows reaction of MTSEA with Y405C and E406C. From these results, we propose that this domain forms a reentrant membrane loop at the cell surface and may comprise part of the translocation pore for substrates and cotransported ions.

journal_name

Neuron

journal_title

Neuron

authors

Seal RP,Amara SG

doi

10.1016/s0896-6273(00)80666-2

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

1487-98

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(00)80666-2

journal_volume

21

pub_type

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