Protein Science

Cover image for Vol. 23 Issue 4

Edited By: Brian W. Matthews

Impact Factor: 2.735

ISI Journal Citation Reports © Ranking: 2012: 150/290 (Biochemistry & Molecular Biology)

Online ISSN: 1469-896X

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  • Mechanisms for regulating deubiquitinating enzymes

    Mechanisms for regulating deubiquitinating enzymes

    Cross-regulation by OTUB1 and E2 enzymes. A: Structure of OTUB1 bound to ubiquitin aldehyde (Ubal) and a UBC13∼Ub conjugate. OTUB1 in this figure is a hybrid containing the catalytic domain of C. elegans OTUB1 and the N-terminal helix of human OTUB1 (4DHZ). B: Superposition of OTUB1 in the presence (green) and absence (gray) of bound ubiquitin. UBC13 shown in blue. Arrows indicate conformational changes in the globular domain (1 and 2) and formation of an N-terminal ubiquitin-binding helix (3) (4DHZ and 4DHI). C: Binding of ubiquitin to distal (top) and proximal (bottom) sites in OTUB1 mimics K48-linked diubiquitin substrate. View of complex in (A) rotated by 90° shows juxtaposition of K48 of proximal ubiquitin and the C-terminus of the distal ubiquitin. D: Structure of OTUB1-Ubal bound to UBCH5B∼Ub (4LDT). View of complex is rotated 180° relative to view of OTUB1-Ubal-UBC13∼Ub complex shown in (C). Surface rendering of OTUB1 C-terminal ubiquitin-binding helix illustrates how this helix, which forms only in OTUB1-E2 complexes containing two bound ubiquitins, forms contacts with both UBCH5B and the proximal ubiquitin. E: Model for regulation of OTUB1 activity in response to changes in ratio of uncharged to charged E2 (E2:E2∼Ub) as well as the concentration of K48-linked polyubiquitin. At low levels of E2 charging (left), E2 binding to OTUB1 stimulates cleavage of K48-linked polyubiquitin. A high proportion of charged E2∼Ub (right), the repressed complex will form between the E2∼Ub, OTUB1 and a free ubiquitin monomer (yellow), which blocks both OTUB1 DUB activity and the ability of the E2 to conjugate ubiquitin to substrate.

  • Mispairs with Watson-Crick base-pair geometry observed in ternary complexes of an RB69 DNA polymerase variant

    Mispairs with Watson‐Crick base‐pair geometry observed in ternary complexes of an RB69 DNA polymerase variant

    Superpositon of the structure of dG/dT (shown in blue) or dT/dG-containing (shown in red) qm with that of dCTP/dG-containing wt RB69 pol (shown in gray). A and B are overlays of dC/dG with dG/dT or dT/dG at position n − 1 respectively; C and D are overlays of dA/dT with dG/dT or dT/dG at position n − 2, respectively. E and F are overlays of dT/dA with dG/dT or dT/dG at position n − 3, respectively. G and H are overlays of dT/dA with dG/dT or dT/dG at position n − 4, respectively. I and J are overlays of dC/dG with dG/dT or dT/dG at position n − 5, respectively.

  • Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families

    Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families

    The trypanosome surface proteins. A: The conservation of the variant surface glycoproteins (VSGs). Residues that are conserved in the A type VSGs are plotted onto the structure of ILTat 1.24 with absolutely conserved residues in red and similar residues in yellow. Conserved residues are predominantly buried in the core of the protein, as seen in the surface representation. B: Alignment of the structures of the VSGs ILTat 1.24 (green) and MITat 1.2 (blue) showing the conserved architecture. C: A comparison of the structures of the VSG ILTat 1.24 and the T. congolense haptoglobin-hemoglobin receptor (HpHbR). Equivalent helices are shown in the same color, indicating the conserved basic architecture of the three helical bundles.

  • Resistance to antibiotics targeted to the bacterial cell wall

    Resistance to antibiotics targeted to the bacterial cell wall

    Schematic model of AmpC β-lactamase induction in Gram-negative organisms. The AmpG–AmpR–AmpC pathway as well as the BlrA/BlrB two component regulatory system are indicated. The presence of β-lactams results in excessive breakdown of the murein sacculus and thus in accumulation of muropeptides. This accumulation causes either the activation of AmpR (AmpG–AmpR–AmpC pathway shown on the left) or the phosphorylation of BlrA (BlrA/BlrB two component regulatory system shown on the right); in both situations, there is induction of the ampC gene. LT, lytic transglycosylase; PBP, Penicillin-Binding Protein.

  • The versatility of the αβ T-cell antigen receptor

    The versatility of the αβ T‐cell antigen receptor

    Comparison of different TCRs binding to pMHC. (A) Alignment (using MHC as the aligning molecule) of a range of previously published TCR-pMHC-I structures (PDB: 3GSN, 3H9S, 3KPS, 3MV7, 1BD2, 1MI5, 1AO7, 2BNR, 1OGA, 2NX5, 2AK4, 3DXA, 3O4L, 1LP9, 3FFC, 3HG1, and 3UTS) (TCRs in multicolored cartoon, pMHC-I in gray cartoon and surface) showing the range of TCR “tilt” relative to the pMHC during binding. (B) Although the TCRα- and β-chains remain in a generally fixed orientation over the pMHC surface (gray cartoon and surface), the positions of the TCR CDR loops (multicolored cartoon) are extremely variable between different TCR-pMHC-I complexes and can bind centrally, or towards the N- or C- terminus of the peptide. (C) Representation of the “swivel” range of docking angles used by TCRs when contacting pMHC surfaces.

  • Signatures of n→π* interactions in proteins

    Signatures of n→π* interactions in proteins

    Experimental electron density around backbone carbonyl groups. (a) Prototypical examples of “gap”, “middle”, and “share” electronic distributions from residues Leu155, Val108, and Leu287 of cholesterol oxidase (PDB: 1n1p), respectively. (b) Relative proportion of “gap”, “middle”, and “share” electronic distributions for residues in cholesterol oxidase that receive an n→π* interaction (n = 50) and those that do not (n = 97).

  • Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal

    Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal

    Binding modes of ethylenediamine-scaffold inhibitor, ED5, and Tipifarnib in A. fumigatus and human protein farnesyltransferases. (A) Inhibitor ED5 contains moieties that bind to the peptide binding site, mobile loop (orange), and the product exit groove. In A. fumigatus farnesyltransferase (AfFTase), ED5 (cyan) binds in the presence of FPP in the active site. In hFTase, ED5 (gray sticks) is competitive with both isoprenoid and peptide substrates, precluding the binding of FPP. In AfFTase, ED5 is competitive with peptide substrate alone. An interactive view is available in the electronic version of the article. (B) The binding mode of tipifarnib in AfFTase (cyan) is conserved with hFTase (gray). In both AfFTase and hFTase, Tipifarnib binds in the presence of FPP (gray, hFTase; cyan, AfFTase). The weaker affinity of Tipifarnib to AfFTase is due to active site widening, as indicated by distances between atoms of the inhibitor and residues that form the active site funnel. Distances are indicated by colored numbers and dashed lines (gray, hFTase; cyan, AfFTase).

  • Mechanisms for regulating deubiquitinating enzymes
  • Mispairs with Watson‐Crick base‐pair geometry observed in ternary complexes of an RB69 DNA polymerase variant
  • Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families
  • Resistance to antibiotics targeted to the bacterial cell wall
  • The versatility of the αβ T‐cell antigen receptor
  • Signatures of n→π* interactions in proteins
  • Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal

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