Year: 2015
Type: article
Abstract: The canonical mechanism for multispanning membrane protein topogenesis suggests that protein topology is established during cotranslational membrane integration. However, this mechanism is inconsistent with the behavior of EmrE, a dual-topology protein for which the mutation of positively charged loop residues, even close to the C-terminus, leads to dramatic shifts in its topology. We use coarse-grained simulations to investigate the Sec-facilitated membrane integration of EmrE and its mutants on realistic biological timescales. This work reveals a mechanism for regulating membrane-protein topogenesis, in which initially misintegrated configurations of the proteins undergo post-translational annealing to reach fully integrated multispanning topologies. The energetic barriers associated with this post-translational annealing process enforce kinetic pathways that dictate the topology of the fully integrated proteins. The proposed mechanism agrees well with the experimentally observed features of EmrE topogenesis and provides a range of experimentally testable predictions regarding the effect of translocon mutations on membrane protein topogenesis.
Source: eLife
DOI: 10.7554/elife.08697
Authors: Reid C Van Lehn, Bin Zhang, Thomas F Miller
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G122673668, G1286236842, G1414775356, G1677143136, G1816284028, G1863003419, G2539837713, G2701020771, G3083819904, G365575497, G382641700, G419881185, G42916606, G4501827968, G498139845, G5076365615, G5094606986, G5296923526, G5854978455, G6786057785, G7652579443, G805243471, Predicting Integral Membrane Protein Expression from Multiscale Simulation Model of Translocon-Mediated Membrane Integration, MRI: Acquisition of a Computer Cluster based on Graphical Processing Units (GPU, G969889393
OpenAlex ID: W2164609757