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  • Journal article
    Garnett JA, Martinez-Santos VI, Saldana Z, Pape T, Hawthorne W, Chan J, Simpson PJ, Cota E, Puente JL, Giron JA, Matthews Set al., 2012,

    Structural insights into the biogenesis and biofilm formation by the <i>Escherichia coli</i> common pilus

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 3950-3955, ISSN: 0027-8424
  • Journal article
    Silhan J, Nagorska K, Zhao Q, Jensen K, Freemont PS, Tang CM, Baldwin GSet al., 2012,

    Specialization of an Exonuclease III family enzyme in the repair of 3' DNA lesions during base excision repair in the human pathogen Neisseria meningitidis

    , Nucleic Acids Research, Vol: 40, Pages: 2065-2075, ISSN: 1362-4962

    We have previously demonstrated that the twoExonuclease III (Xth) family members presentwithin the obligate human pathogen Neisseriameningitidis, NApe and NExo, are important forsurvival under conditions of oxidative stress. Ofthese, only NApe possesses AP endonucleaseactivity, while the primary function of NExoremained unclear. We now reveal further functionalspecialization at the level of 30-PO4 processing forNExo. We demonstrate that the bi-functional meningococcalglycosylases Nth and MutM can performstrand incisions at abasic sites in addition to NApe.However, no such functional redundancy existsfor the 30-phosphatase activity of NExo, and thecytotoxicity of 30-blocking lesions is reflectedin the marked sensitivity of a mutant lackingNExo to oxidative stress, compared to strainsdeficient in other base excision repair enzymes. Ahistidine residue within NExo that is responsiblefor its lack of AP endonuclease activity isalso important for its 30-phosphatase activity,demonstrating an evolutionary trade off in enzymefunction at the single amino acid level. This specializationof two Xth enzymes for the 30-end processingand strand-incision reactions has notpreviously been observed and provides a newparadigm within the prokaryotic world for separationof these critical functions during baseexcision repair.

  • Journal article
    Shah UV, Williams DR, Heng JYY, 2012,

    Selective Crystallization of Proteins Using Engineered Nanonucleants

    , CRYSTAL GROWTH & DESIGN, Vol: 12, Pages: 1362-1369, ISSN: 1528-7483
  • Journal article
    Beeby M, Cho M, Stubbe J, Jensen GJet al., 2012,

    Growth and localization of polyhydroxybutyrate granules in Ralstonia eutropha

    , J. Bacteriol., Vol: 194, Pages: 1092-1099
  • Journal article
    Mckie AB, Vaughan S, Zanini E, Okon IS, Louis L, de Sousa C, Greene MI, Wang Q, Agarwal R, Shaposhnikov D, Wong JLS, Gungor H, Janczar S, El-Bahrawy M, Lam E-F, Chayen NE, Gabra Het al., 2012,

    The OPCML Tumor Suppressor Functions as a Cell Surface Repressor–Adaptor, Negatively Regulating Receptor Tyrosine Kinases in Epithelial Ovarian Cancer

    , Cancer Discovery
  • Journal article
    Murray JW, 2012,

    Sequence variation at the oxygen-evolving centre of photosystem II: a new class of 'rogue' cyanobacterial D1 proteins

    , PHOTOSYNTHESIS RESEARCH, Vol: 110, Pages: 177-184, ISSN: 0166-8595
  • Journal article
    Martino L, Pennell S, Kelly G, Bui TTT, Kotik-Kogan O, Smerdon SJ, Drake AF, Curry S, Conte MRet al., 2012,

    Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein

    , NUCLEIC ACIDS RESEARCH, Vol: 40, Pages: 1381-1394, ISSN: 0305-1048
  • Journal article
    Santabarbara S, Bailleul B, Redding K, Barber J, Rappaport F, Telfer Aet al., 2012,

    Kinetics of phyllosemiquinone oxidation in the Photosystem I reaction centre of <i>Acaryochloris marina</i>

    , BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1817, Pages: 328-335, ISSN: 0005-2728
  • Journal article
    Michoux F, Takasaka K, Boehm M, Komenda J, Nixon PJ, Murray JWet al., 2012,

    Crystal structure of the Psb27 assembly factor at 1.6: implications for binding to Photosystem II

    , PHOTOSYNTHESIS RESEARCH, Vol: 110, Pages: 169-175, ISSN: 0166-8595
  • Journal article
    Smith EJ, Corrigan RM, van der Sluis T, Gruendling A, Speziale P, Geoghegan JA, Foster TJet al., 2012,

    The immune evasion protein Sbi of Staphylococcus aureus occurs both extracellularly and anchored to the cell envelope by binding lipoteichoic acid

    , MOLECULAR MICROBIOLOGY, Vol: 83, Pages: 789-804, ISSN: 0950-382X
  • Journal article
    Quigley A, Williams D, 2012,

    Second Virial Coefficients as Determined using Self Interaction Chromatography and Protein Aggregation in Solution

    , BIOPHYSICAL JOURNAL, Vol: 102, Pages: 442A-442A, ISSN: 0006-3495
  • Journal article
    Bebeacua C, Förster A, McKeown C, Meyer HH, Zhang X, Freemont PSet al., 2012,

    Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy.

    , Proc Natl Acad Sci U S A, Vol: 109, Pages: 1098-1103

    p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly.

  • Journal article
    Smith EJ, Corrigan RM, van der Sluis T, Gründling A, Speziale P, Geoghegan JA, Foster TJet al., 2012,

    The immune evasion protein Sbi of Staphylococcus aureus occurs both extracellularly and anchored to the cell envelope by binding lipoteichoic acid.

    , Mol Microbiol

    The Sbi protein of Staphylococcus aureus comprises two IgG binding domains similar to those of protein A and a region that triggers the activation of complement C3. Sbi is expressed on the cell surface but its C-terminal domain lacks motifs associated with wall or membrane anchoring of proteins in Gram-positive bacteria. Cell-associated Sbi fractionates with the cytoplasmic membrane and is not solubilised during protoplast formation. S.aureus expressing Sbi truncates of the C-terminal Y domain allowed identification of residues that are required for association of Sbi with the membrane. Recombinant Sbi bound to purified cytoplasmic membrane material in vitro and to purified lipoteichoic acid. This explains how Sbi partitions with the membrane in fractionation experiments yet is partially exposed on the cell surface. An LTA-defective mutant of S. aureus had reduced levels of Sbi in the cytoplasmic membrane.

  • Journal article
    Garnett JA, Simpson PJ, Taylor J, Benjamin SV, Tagliaferri C, Cota E, Chen Y-YM, Wu H, Matthews Set al., 2012,

    Structural insight into the role of <i>Streptococcus parasanguinis</i> Fap1 within oral biofilm formation

    , BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 417, Pages: 421-426, ISSN: 0006-291X
  • Conference paper
    Cota E, 2012,

    Candida albicans Als adhesins - New insights from recent structural and functional data

    , 11th ASM Conference on Candida and Candidiasis
  • Journal article
    Cardona T, Sedoud A, Cox N, Rutherford AWet al., 2012,

    Charge separation in Photosystem II: A comparative and evolutionary overview

    , BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1817, Pages: 26-43, ISSN: 0005-2728
  • Journal article
    Govindan S, McElligott A, Muthusamy S, Nair N, Barefield D, Martin JL, Gongora E, Greis KD, Luther PK, Winegrad S, Henderson KK, Sadayappan Set al., 2012,

    Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction

    , JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 52, Pages: 154-164, ISSN: 0022-2828
  • Journal article
    Joly N, Zhang N, Buck M, Zhang Xet al., 2012,

    Coupling AAA protein function to regulated gene expression

    , BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol: 1823, Pages: 108-116, ISSN: 0167-4889
  • Journal article
    Kloppsteck P, Ewens CA, Foerster A, Zhang X, Freemont PSet al., 2012,

    Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family

    , BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol: 1823, Pages: 125-129, ISSN: 0167-4889
  • Journal article
    Dolezal P, Aili M, Tong J, Jiang J-H, Marobbio CM, Lee SF, Schuelein R, Belluzzo S, Binova E, Mousnier A, Frankel G, Giannuzzi G, Palmieri F, Gabriel K, Naderer T, Hartland EL, Lithgow Tet al., 2012,

    <i>Legionella pneumophila</i> Secretes a Mitochondrial Carrier Protein during Infection

    , PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366
  • Journal article
    Komenda J, Knoppova J, Kopecna J, Sobotka R, Halada P, Yu J, Nickelsen J, Boehm M, Nixon PJet al., 2012,

    The Psb27 Assembly Factor Binds to the CP43 Complex of Photosystem II in the Cyanobacterium <i>Synechocystis</i> sp PCC 6803

    , PLANT PHYSIOLOGY, Vol: 158, Pages: 476-486, ISSN: 0032-0889
  • Journal article
    De Simone A, Kitchen C, Kwan A, Sunde M, Dobson CM, Frenkel Det al., 2012,

    Intrinsic Disorder Modulates Protein Self-Assembly and Aggregation

    , Proc Natl Acad Sci U S A, Vol: 109, Pages: 6951-6956
  • Journal article
    Salek-Ardakani S, Cota E, Bignell E, 2012,

    Host-fungal interactions: key players of antifungal immunity.

    , Expert Rev Anti Infect Ther, Vol: 10(2), Pages: 149-151
  • Journal article
    Kim TW, Lee JH, Choi J, Kim KH, van Wilderen LJ, Guerin L, Kim Y, Jung YO, Yang C, Kim J, Wulff M, van Thor JJ, Ihee Het al., 2012,

    Protein Structural Dynamics of Photoactive Yellow Protein in Solution Revealed by Pump−Probe X-ray Solution Scattering.

    , J. Am. Chem. Soc.

    Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump−probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 μs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle.

  • Journal article
    Batty EC, Jensen K, Freemont PS, 2012,

    PML NUCLEAR BODIES AND OTHER TRIM-DEFINED SUBCELLULAR COMPARTMENTS

    , TRIM/RBCC PROTEINS, Vol: 770, Pages: 39-58, ISSN: 0065-2598
  • Journal article
    Lincoln CN, Fitzpatrick AE, van Thor JJ, 2012,

    Photoisomerisation Quantum Yield and Non-linear Cross-Sections with Femtosecond Excitation of the Photoactive Yellow Protein

    , Phys Chem Chem Phys, Pages: 15752-15764
  • Journal article
    Wang GD, Mallet FP, Ricard F, Heng JYYet al., 2012,

    Pharmaceutical nanocrystals

    , Current Opinion in Chemical Engineering, Vol: 1, Pages: 102-107
  • Journal article
    Juozapavicius M, Kaucikas M, van Thor JJ, O'Regan Bet al., 2012,

    Observation of Multi-Exponential Pico to Sub-Nanosecond Electron Injection in Optimized Dye-Sensitized Solar Cells With Visible-Pump Mid-Infrared-Probe Transient Absorption Spectroscopy

    , J. Phys. Chem. C
  • Journal article
    De Simone A, Dhulesia A, Soldi G, Vendruscolo M, Hsu S-TD, Chiti F, Dobson CMet al., 2011,

    Experimental free energy surfaces reveal the mechanisms of maintenance of protein solubility

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 21057-21062, ISSN: 0027-8424
  • Journal article
    Mikkelsen H, McMullan R, Filloux A, 2011,

    The pseudomonas aeruginosa reference strain PA14 displays increased virulence due to a mutation in ladS

    , PLoS ONE, Vol: 6, ISSN: 1932-6203

    Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research.

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