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Wide inward-open liganded UraA in complex with a conformation-selective synthetic nanobodyWide inward-open liganded UraA in complex with a conformation-selective synthetic nanobody
Structural highlights
FunctionURAA_ECOLI Transport of uracil in the cell.[1] [2] Publication Abstract from PubMedUptake of nucleobases and ascorbate is an essential process in all living organisms mediated by SLC23 transport proteins. These transmembrane carriers operate via the elevator alternating-access mechanism, and are composed of two rigid domains whose relative motion drives transport. The lack of large conformational changes within these domains suggests that the interdomain-linkers act as flexible tethers. Here, we show that interdomain-linkers are not mere tethers, but have a key regulatory role in dictating the conformational space of the transporter and defining the rotation axis of the mobile transport domain. By resolving a wide inward-open conformation of the SLC23 elevator transporter UraA and combining biochemical studies using a synthetic nanobody as conformational probe with hydrogen-deuterium exchange mass spectrometry, we demonstrate that interdomain-linkers control the function of transport proteins by influencing substrate affinity and transport rate. These findings open the possibility to allosterically modulate the activity of elevator proteins by targeting their linkers. Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA.,Kuhn BT, Zoller J, Zimmermann I, Gemeinhardt T, Ozkul DH, Langer JD, Seeger MA, Geertsma ER Nat Commun. 2024 Aug 30;15(1):7518. doi: 10.1038/s41467-024-51814-8. PMID:39209842[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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