Abstract:
:Glutamate transporters are essential for recovery of the neurotransmitter glutamate from the synaptic cleft. Crystal structures in the outward- and inward-facing conformations of a glutamate transporter homolog from archaebacterium Pyrococcus horikoshii, sodium/aspartate symporter GltPh, suggested the molecular basis of the transporter cycle. However, dynamic studies of the transport mechanism have been sparse and indirect. Here we present high-speed atomic force microscopy (HS-AFM) observations of membrane-reconstituted GltPh at work. HS-AFM movies provide unprecedented real-space and real-time visualization of the transport dynamics. Our results show transport mediated by large amplitude 1.85-nm "elevator" movements of the transport domains consistent with previous crystallographic and spectroscopic studies. Elevator dynamics occur in the absence and presence of sodium ions and aspartate, but stall in sodium alone, providing a direct visualization of the ion and substrate symport mechanism. We show unambiguously that individual protomers within the trimeric transporter function fully independently.
journal_name
Proc Natl Acad Sci U S Aauthors
Ruan Y,Miyagi A,Wang X,Chami M,Boudker O,Scheuring Sdoi
10.1073/pnas.1616413114subject
Has Abstractpub_date
2017-02-14 00:00:00pages
1584-1588issue
7eissn
0027-8424issn
1091-6490pii
1616413114journal_volume
114pub_type
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