Robert Thompson Clubb

Professor, Chemistry and Biochemistry, University of California Los Angeles

1 (310) 206-0344

Research Summary: Bacterial pathogens mount successful infections by displaying virulence factors that enable them to adhere to host tissues, evade the immune response, invade host cells and acquire essential nutrients. I am interested in understanding the molecular mechanisms that underpin virulence factor display and function, and I hope to translate my laboratory’s research findings into practical applications.

Publications

  1. Cheung NA, Song M, Sue CK, Clubb RT. Quantifying the Kinetics of Pilus-Specific Sortase-Catalyzed Crosslinking Using High-Performance Liquid Chromatography.. Methods in molecular biology (Clifton, N.J.), 2024.
  2. Mahoney BJ, Goring AK, Wang Y, Dasika P, Zhou A, Grossbard E, Cascio D, Loo JA, Clubb RT. Development and atomic structure of a new fluorescence-based sensor to probe heme transfer in bacterial pathogens.. Journal of inorganic biochemistry, 2023.
  3. Sue CK, Cheung NA, Mahoney BJ, McConnell SA, Scully JM, Fu JY, Chang C, Ton-That H, Loo JA, Clubb RT. The basal and major pilins in the Corynebacterium diphtheriae SpaA pilus adopt similar structures that competitively react with the pilin polymerase.. Biopolymers, 2023.
  4. Sue CK, Cheung NA, Mahoney BJ, McConnell SA, Scully JM, Fu JY, Chang C, Ton-That H, Loo JA, Clubb RT. The Basal and Major Pilins in the Corynebacterium diphtheriae SpaA Pilus Adopt Similar Structures that Competitively React with the Pilin Polymerase.. bioRxiv : the preprint server for biology, 2023.
  5. Macdonald R, Mahoney BJ, Soule J, Goring AK, Ford J, Loo JA, Cascio D, Clubb RT. The Shr receptor from Streptococcus pyogenes uses a cap and release mechanism to acquire heme-iron from human hemoglobin.. Proceedings of the National Academy of Sciences of the United States of America, 2023.
  6. Clayton J, Ellis-Guardiola K, Mahoney BJ, Soule J, Liu W, Clubb RT, Wereszczynski J. Directed Inter-domain Motions Enable the IsdH Staphylococcus aureus Receptor to Rapidly Extract Heme from Human Hemoglobin.. Journal of molecular biology, 2022.
  7. Mahoney BJ, Takayesu A, Zhou A, Cascio D, Clubb RT. The structure of the Clostridium thermocellum RsgI9 ectodomain provides insight into the mechanism of biomass sensing.. Proteins, 2022.
  8. Martinez OE, Mahoney BJ, Goring AK, Yi SW, Tran DP, Cascio D, Phillips ML, Muthana MM, Chen X, Jung ME, Loo JA, Clubb RT. Insight into the molecular basis of substrate recognition by the wall teichoic acid glycosyltransferase TagA.. The Journal of biological chemistry, 2021.
  9. Ellis-Guardiola K, Soule J, Clubb RT. Methods for the Extraction of Heme Prosthetic Groups from Hemoproteins.. Bio-protocol, 2021.
  10. McConnell SA, McAllister RA, Amer BR, Mahoney BJ, Sue CK, Chang C, Ton-That H, Clubb RT. Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism.. Proceedings of the National Academy of Sciences of the United States of America, 2021.
  11. Ellis-Guardiola K, Mahoney BJ, Clubb RT. NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin.. Frontiers in microbiology, 2021.
  12. Sue CK, McConnell SA, Ellis-Guardiola K, Muroski JM, McAllister RA, Yu J, Alvarez AI, Chang C, Ogorzalek Loo RR, Loo JA, Ton-That H, Clubb RT. Kinetics and Optimization of the Lysine-Isopeptide Bond Forming Sortase Enzyme from Corynebacterium diphtheriae.. Bioconjugate chemistry, 2020.
  13. Gosschalk JE, Chang C, Sue CK, Siegel SD, Wu C, Kattke MD, Yi SW, Damoiseaux R, Jung ME, Ton-That H, Clubb RT. A Cell-based Screen in Actinomyces oris to Identify Sortase Inhibitors.. Scientific reports, 2020.
  14. McConnell SA, Cannon KA, Morgan C, McAllister R, Amer BR, Clubb RT, Yeates TO. Designed Protein Cages as Scaffolds for Building Multienzyme Materials.. ACS synthetic biology, 2020.
  15. Ellis-Guardiola K, Clayton J, Pham C, Mahoney BJ, Wereszczynski J, Clubb RT. The Staphylococcus aureus IsdH Receptor Forms a Dynamic Complex with Human Hemoglobin that Triggers Heme Release via Two Distinct Hot Spots.. Journal of molecular biology, 2019.
  16. Chang C, Wu C, Osipiuk J, Siegel SD, Zhu S, Liu X, Joachimiak A, Clubb RT, Das A, Ton-That H. Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes.. Proceedings of the National Academy of Sciences of the United States of America, 2019.
  17. Macdonald R, Mahoney BJ, Ellis-Guardiola K, Maresso A, Clubb RT. NMR experiments redefine the hemoglobin binding properties of bacterial NEAr-iron Transporter domains.. Protein science : a publication of the Protein Society, 2019.
  18. Tsui HS, Pham NVB, Amer BR, Bradley MC, Gosschalk JE, Gallagher-Jones M, Ibarra H, Clubb RT, Blaby-Haas CE, Clarke CF. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function.. Journal of lipid research, 2019.
  19. Kattke MD, Gosschalk JE, Martinez OE, Kumar G, Gale RT, Cascio D, Sawaya MR, Philips M, Brown ED, Clubb RT. Structure and mechanism of TagA, a novel membrane-associated glycosyltransferase that produces wall teichoic acids in pathogenic bacteria.. PLoS pathogens, 2019.
  20. Siegel SD, Amer BR, Wu C, Sawaya MR, Gosschalk JE, Clubb RT, Ton-That H. Structure and Mechanism of LcpA, a Phosphotransferase That Mediates Glycosylation of a Gram-Positive Bacterial Cell Wall-Anchored Protein.. mBio, 2019.
  21. Macdonald R, Cascio D, Collazo MJ, Phillips M, Clubb RT. The Streptococcus pyogenes Shr protein captures human hemoglobin using two structurally unique binding domains.. The Journal of biological chemistry, 2018.
  22. McConnell SA, Amer BR, Muroski J, Fu J, Chang C, Ogorzalek Loo RR, Loo JA, Osipiuk J, Ton-That H, Clubb RT. Protein Labeling via a Specific Lysine-Isopeptide Bond Using the Pilin Polymerizing Sortase from Corynebacterium diphtheriae.. Journal of the American Chemical Society, 2018.
  23. Chang C, Amer BR, Osipiuk J, McConnell SA, Huang IH, Hsieh V, Fu J, Nguyen HH, Muroski J, Flores E, Ogorzalek Loo RR, Loo JA, Putkey JA, Joachimiak A, Das A, Clubb RT, Ton-That H. In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.. Proceedings of the National Academy of Sciences of the United States of America, 2018.
  24. Huang GL, Gosschalk JE, Kim YS, Ogorzalek Loo RR, Clubb RT. Stabilizing displayed proteins on vegetative Bacillus subtilis cells.. Applied microbiology and biotechnology, 2018.
  25. Sjodt M, Macdonald R, Marshall JD, Clayton J, Olson JS, Phillips M, Gell DA, Wereszczynski J, Clubb RT. Energetics underlying hemin extraction from human hemoglobin by Staphylococcus aureus.. The Journal of biological chemistry, 2018.
  26. Jacobitz AW, Kattke MD, Wereszczynski J, Clubb RT. Sortase Transpeptidases: Structural Biology and Catalytic Mechanism.. Advances in protein chemistry and structural biology, 2017.
  27. Sjodt M, Clubb RT. Nitroxide Labeling of Proteins and the Determination of Paramagnetic Relaxation Derived Distance Restraints for NMR Studies.. Bio-protocol, 2017.
  28. Chan AH, Yi SW, Weiner EM, Amer BR, Sue CK, Wereszczynski J, Dillen CA, Senese S, Torres JZ, McCammon JA, Miller LS, Jung ME, Clubb RT. NMR structure-based optimization of Staphylococcus aureus sortase A pyridazinone inhibitors.. Chemical biology & drug design, 2017.
  29. Kattke MD, Chan AH, Duong A, Sexton DL, Sawaya MR, Cascio D, Elliot MA, Clubb RT. Crystal Structure of the Streptomyces coelicolor Sortase E1 Transpeptidase Provides Insight into the Binding Mode of the Novel Class E Sorting Signal.. PloS one, 2016.
  30. Jacobitz AW, Naziga EB, Yi SW, McConnell SA, Peterson R, Jung ME, Clubb RT, Wereszczynski J. The "Lid" in the Streptococcus pneumoniae SrtC1 Sortase Adopts a Rigid Structure that Regulates Substrate Access to the Active Site.. The journal of physical chemistry. B, 2016.
  31. Amer BR, Macdonald R, Jacobitz AW, Liauw B, Clubb RT. Rapid addition of unlabeled silent solubility tags to proteins using a new substrate-fused sortase reagent.. Journal of biomolecular NMR, 2016.
  32. Tekeste SS, Wilkinson TA, Weiner EM, Xu X, Miller JT, Le Grice SF, Clubb RT, Chow SA. Interaction between Reverse Transcriptase and Integrase Is Required for Reverse Transcription during HIV-1 Replication.. Journal of virology, 2015.
  33. Chan AH, Yi SW, Terwilliger AL, Maresso AW, Jung ME, Clubb RT. Structure of the Bacillus anthracis Sortase A Enzyme Bound to Its Sorting Signal: A FLEXIBLE AMINO-TERMINAL APPENDAGE MODULATES SUBSTRATE ACCESS.. The Journal of biological chemistry, 2015.
  34. Zilbermintz L, Leonardi W, Jeong SY, Sjodt M, McComb R, Ho CL, Retterer C, Gharaibeh D, Zamani R, Soloveva V, Bavari S, Levitin A, West J, Bradley KA, Clubb RT, Cohen SN, Gupta V, Martchenko M. Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.. Scientific reports, 2015.
  35. Macdonald R, Sarkar D, Amer BR, Clubb RT. Solution structure of the PhoP DNA-binding domain from Mycobacterium tuberculosis.. Journal of biomolecular NMR, 2015.
  36. Dickson CF, Jacques DA, Clubb RT, Guss JM, Gell DA. The structure of haemoglobin bound to the haemoglobin receptor IsdH from Staphylococcus aureus shows disruption of the native α-globin haem pocket.. Acta crystallographica. Section D, Biological crystallography, 2015.
  37. Sjodt M, Macdonald R, Spirig T, Chan AH, Dickson CF, Fabian M, Olson JS, Gell DA, Clubb RT. The PRE-Derived NMR Model of the 38.8-kDa Tri-Domain IsdH Protein from Staphylococcus aureus Suggests That It Adaptively Recognizes Human Hemoglobin.. Journal of molecular biology, 2015.
  38. Zhang J, Reza Malmirchegini G, Clubb RT, Loo JA. Native top-down mass spectrometry for the structural characterization of human hemoglobin.. European journal of mass spectrometry (Chichester, England), 2015.
  39. Amer BR, Clubb RT. A sweet new role for LCP enzymes in protein glycosylation.. Molecular microbiology, 2014.
  40. Malmirchegini GR, Sjodt M, Shnitkind S, Sawaya MR, Rosinski J, Newton SM, Klebba PE, Clubb RT. Novel mechanism of hemin capture by Hbp2, the hemoglobin-binding hemophore from Listeria monocytogenes.. The Journal of biological chemistry, 2014.
  41. Wolahan SM, Li Z, Hsu CH, Huang SJ, Clubb R, Hwang LP, Lin YY. A robust approach to correct for pronounced errors in temperature measurements by controlling radiation damping feedback fields in solution NMR.. Journal of magnetic resonance (San Diego, Calif. : 1997), 2014.
  42. Twu O, Dessí D, Vu A, Mercer F, Stevens GC, de Miguel N, Rappelli P, Cocco AR, Clubb RT, Fiori PL, Johnson PJ. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.. Proceedings of the National Academy of Sciences of the United States of America, 2014.
  43. Jacobitz AW, Wereszczynski J, Yi SW, Amer BR, Huang GL, Nguyen AV, Sawaya MR, Jung ME, McCammon JA, Clubb RT. Structural and computational studies of the Staphylococcus aureus sortase B-substrate complex reveal a substrate-stabilized oxyanion hole.. The Journal of biological chemistry, 2014.
  44. Dickson CF, Kumar KK, Jacques DA, Malmirchegini GR, Spirig T, Mackay JP, Clubb RT, Guss JM, Gell DA. Structure of the hemoglobin-IsdH complex reveals the molecular basis of iron capture by Staphylococcus aureus.. The Journal of biological chemistry, 2014.
  45. Huang GL, Anderson TD, Clubb RT. Engineering microbial surfaces to degrade lignocellulosic biomass.. Bioengineered, 2013.
  46. Chan AH, Wereszczynski J, Amer BR, Yi SW, Jung ME, McCammon JA, Clubb RT. Discovery of Staphylococcus aureus sortase A inhibitors using virtual screening and the relaxed complex scheme.. Chemical biology & drug design, 2013.
  47. Ran Y, Malmirchegini GR, Clubb RT, Lei B. Axial ligand replacement mechanism in heme transfer from streptococcal heme-binding protein Shp to HtsA of the HtsABC transporter.. Biochemistry, 2013.
  48. Kappel K, Wereszczynski J, Clubb RT, McCammon JA. The binding mechanism, multiple binding modes, and allosteric regulation of Staphylococcus aureus Sortase A probed by molecular dynamics simulations.. Protein science : a publication of the Protein Society, 2012.
  49. Spirig T, Malmirchegini GR, Zhang J, Robson SA, Sjodt M, Liu M, Krishna Kumar K, Dickson CF, Gell DA, Lei B, Loo JA, Clubb RT. Staphylococcus aureus uses a novel multidomain receptor to break apart human hemoglobin and steal its heme.. The Journal of biological chemistry, 2012.
  50. Robson SA, Jacobitz AW, Phillips ML, Clubb RT. Solution structure of the sortase required for efficient production of infectious Bacillus anthracis spores.. Biochemistry, 2012.
  51. Sam MD, Clubb RT. Preparation and optimization of protein-DNA complexes suitable for detailed NMR studies.. Methods in molecular biology (Clifton, N.J.), 2012.
  52. Spirig T, Clubb RT. Backbone 1H, 13C and 15N resonance assignments of the 39 kDa staphylococcal hemoglobin receptor IsdH.. Biomolecular NMR assignments, 2011.
  53. Spirig T, Weiner EM, Clubb RT. Sortase enzymes in Gram-positive bacteria.. Molecular microbiology, 2011.
  54. Krishna Kumar K, Jacques DA, Pishchany G, Caradoc-Davies T, Spirig T, Malmirchegini GR, Langley DB, Dickson CF, Mackay JP, Clubb RT, Skaar EP, Guss JM, Gell DA. Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH.. The Journal of biological chemistry, 2011.
  55. Villareal VA, Spirig T, Robson SA, Liu M, Lei B, Clubb RT. Transient weak protein-protein complexes transfer heme across the cell wall of Staphylococcus aureus.. Journal of the American Chemical Society, 2011.
  56. Januszyk K, Fleissner MR, Atchabahian L, Shieh FK, Altenbach C, Martin SL, Guo F, Hubbell WL, Clubb RT. Site-directed spin labeling electron paramagnetic resonance study of the ORF1 protein from a mouse L1 retrotransposon.. Protein science : a publication of the Protein Society, 2011.
  57. Ramey JD, Villareal VA, Ng C, Ward SC, Xiong JP, Clubb RT, Bradley KA. Anthrax toxin receptor 1/tumor endothelial marker 8: mutation of conserved inserted domain residues overrides cytosolic control of protective antigen binding.. Biochemistry, 2010.
  58. Robson SA, Peterson R, Bouchard LS, Villareal VA, Clubb RT. A heteronuclear zero quantum coherence Nz-exchange experiment that resolves resonance overlap and its application to measure the rates of heme binding to the IsdC protein.. Journal of the American Chemical Society, 2010.
  59. Senturia R, Faller M, Yin S, Loo JA, Cascio D, Sawaya MR, Hwang D, Clubb RT, Guo F. Structure of the dimerization domain of DiGeorge critical region 8.. Protein science : a publication of the Protein Society, 2010.
  60. Weiner EM, Robson S, Marohn M, Clubb RT. The Sortase A enzyme that attaches proteins to the cell wall of Bacillus anthracis contains an unusual active site architecture.. The Journal of biological chemistry, 2010.
  61. Suree N, Yi SW, Thieu W, Marohn M, Damoiseaux R, Chan A, Jung ME, Clubb RT. Discovery and structure-activity relationship analysis of Staphylococcus aureus sortase A inhibitors.. Bioorganic & medicinal chemistry, 2009.
  62. Suree N, Liew CK, Villareal VA, Thieu W, Fadeev EA, Clemens JJ, Jung ME, Clubb RT. The structure of the Staphylococcus aureus sortase-substrate complex reveals how the universally conserved LPXTG sorting signal is recognized.. The Journal of biological chemistry, 2009.
  63. Fadeev EA, Sam MD, Clubb RT. NMR structure of the amino-terminal domain of the lambda integrase protein in complex with DNA: immobilization of a flexible tail facilitates beta-sheet recognition of the major groove.. Journal of molecular biology, 2009.
  64. Wilkinson TA, Januszyk K, Phillips ML, Tekeste SS, Zhang M, Miller JT, Le Grice SF, Clubb RT, Chow SA. Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase.. The Journal of biological chemistry, 2009.
  65. Pilpa RM, Robson SA, Villareal VA, Wong ML, Phillips M, Clubb RT. Functionally distinct NEAT (NEAr Transporter) domains within the Staphylococcus aureus IsdH/HarA protein extract heme from methemoglobin.. The Journal of biological chemistry, 2008.
  66. Villareal VA, Pilpa RM, Robson SA, Fadeev EA, Clubb RT. The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme.. The Journal of biological chemistry, 2008.
  67. Yeates TO, Clubb RT. Biochemistry. How some pili pull.. Science (New York, N.Y.), 2007.
  68. Januszyk K, Li PW, Villareal V, Branciforte D, Wu H, Xie Y, Feigon J, Loo JA, Martin SL, Clubb RT. Identification and solution structure of a highly conserved C-terminal domain within ORF1p required for retrotransposition of long interspersed nuclear element-1.. The Journal of biological chemistry, 2007.
  69. Abbani MA, Papagiannis CV, Sam MD, Cascio D, Johnson RC, Clubb RT. Structure of the cooperative Xis-DNA complex reveals a micronucleoprotein filament that regulates phage lambda intasome assembly.. Proceedings of the National Academy of Sciences of the United States of America, 2007.
  70. Papagiannis CV, Sam MD, Abbani MA, Yoo D, Cascio D, Clubb RT, Johnson RC. Fis targets assembly of the Xis nucleoprotein filament to promote excisive recombination by phage lambda.. Journal of molecular biology, 2007.
  71. Sam MD, Abbani MA, Cascio D, Johnson RC, Clubb RT. Crystallization, dehydration and preliminary X-ray analysis of excisionase (Xis) proteins cooperatively bound to DNA.. Acta crystallographica. Section F, Structural biology and crystallization communications, 2006.
  72. Pilpa RM, Fadeev EA, Villareal VA, Wong ML, Phillips M, Clubb RT. Solution structure of the NEAT (NEAr Transporter) domain from IsdH/HarA: the human hemoglobin receptor in Staphylococcus aureus.. Journal of molecular biology, 2006.
  73. Jung ME, Clemens JJ, Suree N, Liew CK, Pilpa R, Campbell DO, Clubb RT. Synthesis of (2R,3S) 3-amino-4-mercapto-2-butanol, a threonine analogue for covalent inhibition of sortases.. Bioorganic & medicinal chemistry letters, 2005.
  74. Naik MT, Suree N, Ilangovan U, Liew CK, Thieu W, Campbell DO, Clemens JJ, Jung ME, Clubb RT. Staphylococcus aureus Sortase A transpeptidase. Calcium promotes sorting signal binding by altering the mobility and structure of an active site loop.. The Journal of biological chemistry, 2005.
  75. Pilpa RM, Clubb RT. NMR resonance assignments of the NEAT (NEAr Transporter) domain from the Staphylococcus aureus IsdH protein.. Journal of biomolecular NMR, 2005.
  76. Iwahara J, Peterson RD, Clubb RT. Compensating increases in protein backbone flexibility occur when the Dead ringer AT-rich interaction domain (ARID) binds DNA: a nitrogen-15 relaxation study.. Protein science : a publication of the Protein Society, 2005.
  77. Abbani M, Iwahara M, Clubb RT. The structure of the excisionase (Xis) protein from conjugative transposon Tn916 provides insights into the regulation of heterobivalent tyrosine recombinases.. Journal of molecular biology, 2005.
  78. Liew CK, Smith BT, Pilpa R, Suree N, Ilangovan U, Connolly KM, Jung ME, Clubb RT. Localization and mutagenesis of the sorting signal binding site on sortase A from Staphylococcus aureus.. FEBS letters, 2004.
  79. Comfort D, Clubb RT. A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria.. Infection and immunity, 2004.
  80. Sam MD, Cascio D, Johnson RC, Clubb RT. Crystal structure of the excisionase-DNA complex from bacteriophage lambda.. Journal of molecular biology, 2004.
  81. Sam MD, Cascio D, Johnson R, Clubb RT. Crystallization and preliminary X-ray crystallographic analysis of the excisionase-DNA complex from bacteriophage lambda.. Acta crystallographica. Section D, Biological crystallography, 2003.
  82. Warren D, Sam MD, Manley K, Sarkar D, Lee SY, Abbani M, Wojciak JM, Clubb RT, Landy A. Identification of the lambda integrase surface that interacts with Xis reveals a residue that is also critical for Int dimer formation.. Proceedings of the National Academy of Sciences of the United States of America, 2003.
  83. Connolly KM, Smith BT, Pilpa R, Ilangovan U, Jung ME, Clubb RT. Sortase from Staphylococcus aureus does not contain a thiolate-imidazolium ion pair in its active site.. The Journal of biological chemistry, 2003.
  84. Milev S, Gorfe AA, Karshikoff A, Clubb RT, Bosshard HR, Jelesarov I. Energetics of sequence-specific protein-DNA association: binding of integrase Tn916 to its target DNA.. Biochemistry, 2003.
  85. Milev S, Gorfe AA, Karshikoff A, Clubb RT, Bosshard HR, Jelesarov I. Energetics of sequence-specific protein-DNA association: conformational stability of the DNA binding domain of integrase Tn916 and its cognate DNA duplex.. Biochemistry, 2003.
  86. Sam MD, Papagiannis CV, Connolly KM, Corselli L, Iwahara J, Lee J, Phillips M, Wojciak JM, Johnson RC, Clubb RT. Regulation of directionality in bacteriophage lambda site-specific recombination: structure of the Xis protein.. Journal of molecular biology, 2002.
  87. Connolly KM, Iwahara M, Clubb RT. Xis protein binding to the left arm stimulates excision of conjugative transposon Tn916.. Journal of bacteriology, 2002.
  88. Wojciak JM, Sarkar D, Landy A, Clubb RT. Arm-site binding by lambda -integrase: solution structure and functional characterization of its amino-terminal domain.. Proceedings of the National Academy of Sciences of the United States of America, 2002.
  89. Iwahara J, Iwahara M, Daughdrill GW, Ford J, Clubb RT. The structure of the Dead ringer-DNA complex reveals how AT-rich interaction domains (ARIDs) recognize DNA.. The EMBO journal, 2002.