5uhs
From Proteopedia
Structure of a SemiSWEET D57A mutant
Structural highlights
Function[SWEET_LEPBP] The homodimer mediates transmembrane sugar transport down a concentration gradient. Transport is probably effected by rocking-type movements, where a cargo-binding cavity opens first on one and then on the other side of the membrane.[1] Publication Abstract from PubMedTransporters shuttle molecules across cell membranes by alternating among distinct conformational states. Fundamental questions remain about how transporters transition between states and how such structural rearrangements regulate substrate translocation. Here, we capture the translocation process by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure reported here spontaneously adopt occluded and inward-open conformations. Strikingly, these conformations match crystal structures, including our inward-open structure. Mutagenesis experiments further validate simulation predictions. Our results reveal that state transitions are driven by favorable interactions formed upon closure of extracellular and intracellular "gates" and by an unfavorable transmembrane helix configuration when both gates are closed. This mechanism leads to tight allosteric coupling between gates, preventing them from opening simultaneously. Interestingly, the substrate appears to take a "free ride" across the membrane without causing major structural rearrangements in the transporter. Mechanism of Substrate Translocation in an Alternating Access Transporter.,Latorraca NR, Fastman NM, Venkatakrishnan AJ, Frommer WB, Dror RO, Feng L Cell. 2017 Mar 23;169(1):96-107.e12. doi: 10.1016/j.cell.2017.03.010. PMID:28340354[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||
