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Structural basis for amino acid transport by the CAT family of SLC7 transporters

Abstract:
Amino acids play essential roles in cell biology as regulators of metabolic pathways. Arginine in particular is a major signalling molecule inside the cell, being a precursor for both l-ornithine and nitric oxide (NO) synthesis and a key regulator of the mTORC1 pathway. In mammals, cellular arginine availability is determined by members of the solute carrier (SLC) 7 family of cationic amino acid transporters. Whereas CAT-1 functions to supply cationic amino acids for cellular metabolism, CAT-2A and -2B are required for macrophage activation and play important roles in regulating inflammation. Here, we present the crystal structure of a close homologue of the mammalian CAT transporters that reveals how these proteins specifically recognise arginine. Our structural and functional data provide a model for cationic amino acid transport in mammalian cells and reveals mechanistic insights into proton-coupled, sodium-independent amino acid transport in the wider APC superfamily.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-018-03066-6

Authors

More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Biochemistry
Role:
Author
ORCID:
0000-0002-2850-5911
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Oxford college:
Christ Church
Role:
Author
ORCID:
0000-0001-7432-2270


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
9
Issue:
1
Pages:
Article number 550
Publication date:
2018-02-07
Acceptance date:
2018-01-17
DOI:
EISSN:
2041-1723
Pmid:
29416041


Language:
English
Keywords:
Pubs id:
pubs:824950
UUID:
uuid:746c26ce-b16d-4136-b96f-95611dde57df
Local pid:
pubs:824950
Source identifiers:
824950
Deposit date:
2018-08-11
ARK identifier:

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