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

Franke, Barbara (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Liverpool, UK
Gasch, Alexander (författare)
Institut für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
Rodriguez, Dayté (författare)
Instituto de Biología Molecular de Barcelona, Barcelona Science Park, Barcelona, Spain
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Chami, Mohamed (författare)
Center for Cellular Imaging and Nanoanalytics (C-CINA), Biozentrum, University of Basel, Basel, Switzerland
Khan, Muzamil M (författare)
Institut für Toxikologie und Genetik, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany
Rudolf, Rüdiger (författare)
Institut für Toxikologie und Genetik, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany; Institut für Zell- und Molekularbiologie, University of Applied Sciences Mannheim, Mannheim, Germany
Bibby, Jaclyn (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, UK
Hanashima, Akira (författare)
Institut für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
Bogomolovas, Julijus (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, UK; Institut für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
von Castelmur, Eleonore (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, UK
Rigden, Daniel J (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, UK
Uson, Isabel (författare)
Instituto de Biología Molecular de Barcelona, Barcelona Science Park, Barcelona, Spain
Labeit, Siegfried (författare)
Institut für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Mannheim, Mannheim, Germany
Mayans, Olga (författare)
Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, UK
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 (creator_code:org_t)
2014-03
2014
Engelska.
Ingår i: Open Biology. - London, United Kingdom : The Royal Society Publishing. - 2046-2441. ; 4
Relaterad länk:
https://liu.diva-por... (primary) (Raw object)
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http://rsob.royalsoc...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Nyckelord

COS-box
RBCC/TRIM fold
X-ray crystallography
ab initio modelling
coiled-coil
electron microscopy

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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