Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold.
The B-box motif is the defining feature of the TRIM family of proteins, characterized by a RING finger-B-box-coiled coil tripartite fold. We have elucidated the crystal structure of B-box 2 (B2) from MuRF1, a TRIM protein that supports a wide variety of protein interactions in the sarcomere and regulates the trophic state of striated muscle tissue. MuRF1 B2 coordinates two zinc ions through a cross-brace alpha/beta-topology typical of members of the RING finger superfamily. However, it self-associates into dimers with high affinity. The dimerization pattern is mediated by the helical component of this fold and is unique among RING-like folds. This B2 reveals a long shallow groove that encircles the C-terminal metal binding site ZnII and appears as the defining protein-protein interaction feature of this domain. A cluster of conserved hydrophobic residues in this groove and, in particular, a highly conserved aromatic residue (Y133 in MuRF1 B2) is likely to be central to this role. We expect these findings to aid the future exploration of the cellular function and therapeutic potential of MuRF1.
Mrosek
Michael
M
Division of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Meier
Sebastian
S
Ucurum-Fotiadis
Zöhre
Z
von Castelmur
Eleonore
E
Hedbom
Erik
E
Lustig
Ariel
A
Grzesiek
Stephan
S
Labeit
Dietmar
D
Labeit
Siegfried
S
Mayans
Olga
O
D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014461:Ultracentrifugation; D015032:Zinc / Q000378:metabolism
D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D015032:Zinc