Structural analysis of B-box 2 from MuRF1: Identification of a novel self-association pattern in a RING-like fold

Michael Mrosek, Sebastian Meier, Zoehre Ucurum-Fotiadis, Eleonore von Castelmur, Erik Hedbom, Ariel Lustig, Stephan Grzesiek, Dietmar Labeit, Siegfried Labeit, Olga Mayans

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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 (132) 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 132 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.
Original languageEnglish
JournalBiochemistry
Volume47
Issue number40
Pages (from-to)10722-10730
Number of pages9
ISSN0006-2960
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • PROTEINS
  • Amino Acid Sequence
  • Chromatography, Gel
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Muscle Proteins
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligases
  • Ultracentrifugation
  • Zinc
  • EC 6.3.2.19 TRIM63 protein, human
  • EC 6.3.2.19 Ubiquitin-Protein Ligases
  • J41CSQ7QDS Zinc
  • Association reactions
  • Binding energy
  • Binding sites
  • Flow interactions
  • Muscle
  • Oligomers
  • Structural analysis
  • Crystal structure
  • muscle RING finger 1 protein
  • zinc ion
  • article
  • B Box motif
  • binding site
  • crystal structure
  • dimerization
  • gel permeation chromatography
  • light scattering
  • priority journal
  • protein folding
  • protein protein interaction
  • protein quaternary structure
  • RING finger motif
  • sarcomere
  • ultracentrifugation
  • Aromatic residues
  • Cellular functions
  • Coiled coils
  • High affinity
  • Hydrophobic residues
  • Metal-binding sites
  • Muscle tissues
  • Protein interactions
  • Protein-protein interaction
  • Ring fingers
  • Self associations
  • Trophic states
  • Zinc ions
  • BIOCHEMISTRY
  • E3 UBIQUITIN LIGASES
  • ZINC-BINDING DOMAIN
  • CRYSTAL-STRUCTURE
  • U-BOX
  • M-LINE
  • B-BOX
  • PROTEIN
  • FINGER
  • REVEALS
  • COMPLEX
  • cellular function
  • dimerization pattern
  • protein-protein interaction
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • MuRFI B-box 2 crystal structure
  • RING finger superfamily
  • TRIM B-box motif
  • zinc ion 23713-49-7
  • 10060, Biochemistry studies - General
  • 10069, Biochemistry studies - Minerals
  • 17504, Muscle - Physiology and biochemistry
  • striated muscle muscular system
  • Biochemistry and Molecular Biophysics

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