Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Jun 2024
29 Jun 2024
Historique:
received:
24
05
2023
accepted:
16
05
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
1
7
2024
Statut:
epublish
Résumé
Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.
Identifiants
pubmed: 38951531
doi: 10.1038/s41467-024-48921-x
pii: 10.1038/s41467-024-48921-x
doi:
Substances chimiques
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Proline
9DLQ4CIU6V
ACE2 protein, human
EC 3.4.17.23
SLC6A19 protein, human
0
Amino Acid Transport Systems, Neutral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5503Subventions
Organisme : Innovative Medicines Initiative (IMI)
ID : 875510
Organisme : Innovative Medicines Initiative (IMI)
ID : 875510
Organisme : Innovative Medicines Initiative (IMI)
ID : 875510
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V018051/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V018051/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V018051/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V018051/1
Informations de copyright
© 2024. The Author(s).
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