2gbr | pdb_00002gbr
Crystal Structure of the 35-36 MoaD Insertion Mutant of Ubiquitin
Structural highlights
FunctionUBC_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe previously concluded that, judging from NMR chemical shifts, the effects of insertions into ubiquitin on its conformation appear to depend primarily on the site of insertion rather than the sequence of the insertion. To obtain a more complete and atomic-resolution understanding of how these insertions modulate the conformation of ubiquitin, we have solved the crystal structures of four insertional mutants of ubiquitin. Insertions between residues 9 and 10 of ubiquitin are minimally perturbing to the remainder of the protein, while larger alterations occur when the insertion is between residues 35 and 36. Further, the alterations in response to insertions are very similar for each mutant at a given site. Two insertions, one at each site, were designed from structurally homologous proteins. Interestingly, the secondary structure within these five to seven amino acid residue insertions is conserved in the new protein. Overall, the crystal structures support the previous conclusion that the conformational effects of these insertions are determined largely by the site of insertion and only secondarily by the sequence of the insert. Structures of ubiquitin insertion mutants support site-specific reflex response to insertions hypothesis.,Ferraro DM, Ferraro DJ, Ramaswamy S, Robertson AD J Mol Biol. 2006 Jun 2;359(2):390-402. Epub 2006 Apr 5. PMID:16647719[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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