Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast

Autor: Zhang, Y., Laurentiis, E., Bohnsack, K., Wahlig, M., Ranjan, N., Gruseck, S., Hackert, P., Wölfle, T., Rodnina, M., Schwappach, B., Rospert, S.
Rok vydání: 2020
Předmět:
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021)
ISSN: 2041-1723
Popis: The guided entry of tail-anchored proteins (GET) pathway assists in the posttranslational delivery of tail-anchored proteins, containing a single C-terminal transmembrane domain, to the ER. Here we uncover how the yeast GET pathway component Get4/5 facilitates capture of tail-anchored proteins by Sgt2, which interacts with tail-anchors and hands them over to the targeting component Get3. Get4/5 binds directly and with high affinity to ribosomes, positions Sgt2 close to the ribosomal tunnel exit, and facilitates the capture of tail-anchored proteins by Sgt2. The contact sites of Get4/5 on the ribosome overlap with those of SRP, the factor mediating cotranslational ER-targeting. Exposure of internal transmembrane domains at the tunnel exit induces high-affinity ribosome binding of SRP, which in turn prevents ribosome binding of Get4/5. In this way, the position of a transmembrane domain within nascent ER-targeted proteins mediates partitioning into either the GET or SRP pathway directly at the ribosomal tunnel exit.
The guided entry of tail-anchored proteins (GET) pathway assists in the delivery of such proteins to the ER. Here, the authors reveal that the pathway components Get4/5 probe a region near the ribosomal exit tunnel. Upon emergence of a client protein, Get4/5 recruits Sgt2 and initiates the targeting phase of the pathway.
Databáze: OpenAIRE