6/24/2023 0 Comments Multipass protein![]() Luka discovered that the first TMD engages the PAT complex, which Min’s structure showed was positioned behind Sec61. Their combined efforts not only led to a better understanding of the PAT complex, but also suggested a completely new model for how multipass proteins are made. In parallel, Min Kyung Kim, a postdoc, used electron cryo-microscopy (cryo-EM) to visualize the PAT complex during Rhodopsin insertion. Luka Smalinskaitė, a PhD student, used biochemical assays to investigate PAT complex function. To address this, Manu’s group took a two-pronged strategy. Although the PAT complex was shown to facilitate the biogenesis of Rhodopsin and several other multipass proteins, how it worked was not known. In earlier work, they discovered the chaperone, termed the PAT complex, that interacts with Rhodopsin as it is being inserted and folded. ![]() Manu’s group investigated this problem by studying the biogenesis of Rhodopsin, a multipass protein that detects light to enable vision. It has been assumed that multipass proteins also rely on Sec61’s lateral gate for insertion, but this was not tested experimentally. Sec61 is well established as the channel for protein secretion, and experiments with single-TMD membrane proteins showed Sec61 can also work for their insertion. In this model, each TMD successively passes through a lateral gate in the protein translocation channel called Sec61. New research from Manu Hegde’s group in the LMB’s Cell Biology Division, in collaboration with Robert Keenan’s lab at the University of Chicago, now sheds light on the fundamental problem of multipass membrane protein biogenesis.įor decades, the prevailing model has been that multipass proteins are weaved into the membrane iteratively, one transmembrane domain (TMD) at a time. Despite their central importance for human physiology, it is unclear how they are correctly inserted into the membrane. Some examples of the many multipass proteins include ion channels, signalling proteins, such as G-protein coupled receptors (GPCRs), and nutrient transporters. Most of these proteins weave back and forth across the membrane multiple times, and are called multipass proteins. New experimentally validated model reveals the key factors and steps used by cells to embed multipass proteins into their membranes Structural model for the multipass translocon bound to a translating ribosome at the endoplasmic reticulum membrane, where membrane proteins are made.Īround one-fourth of all human genes code for membrane-embedded proteins.
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