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Structural basis for membrane protein biogenesis at the Endoplasmic reticulum by the SND pathway

Objective

One-third of eukaryotic genes encode for integral membrane proteins (IMPs) with the majority being assembled at the endoplasmic reticulum (ER) after being translated by the ribosome. The SRP-independent (SND) targeting pathway was recently identified as a new route for ER targeting and insertion of IMPs. It was found to recognise a subset of IMPs with a central transmembrane domain, yet it also serves as an alternative route to deliver a broad range of substrates to the ER when their canonical pathways are impaired. The yeast SND pathway comprises three components, SND1, SND2 and SND3. The cytosolic SND1 is a putative ribosome-associated factor and receptor for nascent IMP substrates. SND2 and SND3 are proposed to form a heterodimeric complex at the ER membrane that, together with the SEC61 translocon, mediates membrane insertion of substrates. However, direct evidence for the roles of the SND components and their physical interactions with each other and complexes such as the ribosome and the SEC61 translocon is lacking.
This project aims to elucidate the molecular interplays between SND components and other targeting and insertion factors using a combination of structural biology, biophysics, and biochemistry. First, I will establish a genomic tagging system to purify SND complexes from Chaetomium thermophilum. I will integrate mass spectrometry and different biophysical tools to identify and subsequently characterise the interactions between SND components and their associated proteins involved in ER membrane targeting and insertion, or potentially other novel biological functions. Ultimately, I will solve the structures of endogenous SND complexes by cryo-electron microscopy. This work will provide comprehensive insights into how the SND complexes capture a broad range of substrates and execute their ER membrane targeting and insertion, and will thus have far-reaching impacts on our current understanding of membrane protein biology.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 189 687,36
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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