RT Journal Article
SR Electronic
T1 Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.05.17.541173
DO 10.1101/2023.05.17.541173
A1 Huanyu Z. Li
A1 Ashley C.W. Pike
A1 Gamma Chi
A1 Jesper S. Hansen
A1 Sarah G. Lee
A1 Karin E.J. Rödström
A1 Simon R. Bushell
A1 David Speedman
A1 Adam Evans
A1 Dong Wang
A1 Didi He
A1 Leela Shrestha
A1 Chady Nasrallah
A1 Nicola A. Burgess-Brown
A1 Timothy R. Dafforn
A1 Elisabeth P. Carpenter
A1 David B. Sauer
YR 2023
UL http://biorxiv.org/content/early/2023/05/18/2023.05.17.541173.abstract
AB 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 which link substrate release and opening of the cytoplasmic gate, and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.Competing Interest StatementThe authors have declared no competing interest.