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Molecular basis for the fold organization and sarcomeric targeting of the muscle atrogin MuRF1

Franke, Barbara and Gasch, Alexander and Rodriguez, Dayté and Chami, Mohamed and Khan, Muzamil M. and Rudolf, Rüdiger and Bibby, Jaclyn and Hanashima, Akira and Bogomolovas, Julijus and von Castelmur, Eleonore and Rigden, Daniel J. and Uson, Isabel and Labeit, Siegfried and Mayans, Olga. (2014) Molecular basis for the fold organization and sarcomeric targeting of the muscle atrogin MuRF1. Open biology, 4. p. 130172.

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Abstract

MuRF1 is an E3 ubiquitin ligase central to muscle catabolism. It belongs to the TRIM protein family characterized by a tripartite fold of RING, B-box and coiled-coil (CC) motifs, followed by variable C-terminal domains. The CC motif is hypothesized to be responsible for domain organization in the fold as well as for high-order assembly into functional entities. But data on CC from this family that can clarify the structural significance of this motif are scarce. We have characterized the helical region from MuRF1 and show that, contrary to expectations, its CC domain assembles unproductively, being the B2- and COS-boxes in the fold (respectively flanking the CC) that promote a native quaternary structure. In particular, the C-terminal COS-box seemingly forms an α-hairpin that packs against the CC, influencing its dimerization. This shows that a C-terminal variable domain can be tightly integrated within the conserved TRIM fold to modulate its structure and function. Furthermore, data from transfected muscle show that in MuRF1 the COS-box mediates the in vivo targeting of sarcoskeletal structures and points to the pharmacological relevance of the COS domain for treating MuRF1-mediated muscle atrophy.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Engel)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > BioEM Lab (Chami)
UniBasel Contributors:Chami, Mohamed
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2046-2441
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:09 Mar 2022 10:28
Deposited On:09 Mar 2022 10:28

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