John Gross, PhD
Professor
Pharmaceutical Chemistry
School of Pharmacy

We use tools from molecular biophysics to understand the structure and regulatory conformational dynamics in these systems with the ultimate goal of defining molecular mechanisms and avenues for structure based drug design.

• Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis.
  Structure (London, England : 1993) 2022 Peters JK, Tibble RW, Warminski M, Jemielity J, Gross JD
• SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
  bioRxiv : the preprint server for biology 2022 Walter M, Chen IP, Vallejo-Gracia A, Kim IJ, Bielska O, Lam VL, Hayashi JM, Cruz A, Shah S, Gross JD, Krogan NJ, Schilling B, Ott M, Verdin E
• Identification of recombinant Fabs for structural and functional characterization of HIV-host factor complexes.
  PloS one 2021 Sevillano N, Green EM, Votteler J, Kim DY, Ren X, Yang B, Liu X, Lourenço AL, Hurley JH, Farr-Jones S, Gross JD, Cheng Y, Craik CS
• Biomolecular condensates amplify mRNA decapping by biasing enzyme conformation.
  Nature chemical biology 2021 Tibble RW, Depaix A, Kowalska J, Jemielity J, Gross JD
• Structural Insights into the Interaction of Clinically Relevant Phosphorothioate mRNA Cap Analogs with Translation Initiation Factor 4E Reveal Stabilization via Electrostatic Thio-Effect.
  ACS chemical biology 2021 Warminski M, Kowalska J, Nowak E, Kubacka D, Tibble R, Kasprzyk R, Sikorski PJ, Gross JD, Nowotny M, Jemielity J
• Pdc2/Pat1 increases the range of decay factors and RNA bound by the Lsm1-7 complex.
  RNA (New York, N.Y.) 2020 Lobel JH, Gross JD
• Biophysical Properties of HP1-Mediated Heterochromatin.
  Cold Spring Harbor symposia on quantitative biology 2020 Sanulli S, Gross JD, Narlikar GJ
• A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
  Nature 2020 Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, …
• Structural Basis for a Species-Specific Determinant of an SIV Vif Protein toward Hominid APOBEC3G Antagonism.
  Cell host & microbe 2019 Binning JM, Chesarino NM, Emerman M, Gross JD
• Pat1 activates late steps in mRNA decay by multiple mechanisms.
  Proceedings of the National Academy of Sciences of the United States of America 2019 Lobel JH, Tibble RW, Gross JD
• HP1 reshapes nucleosome core to promote phase separation of heterochromatin.
  Nature 2019 Sanulli S, Trnka MJ, Dharmarajan V, Tibble RW, Pascal BD, Burlingame AL, Griffin PR, Gross JD, Narlikar GJ
• ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
  Cell host & microbe 2019 Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ
• Conformational Dynamics of the HIV-Vif Protein Complex.
  Biophysical journal 2019 Ball KA, Chan LM, Stanley DJ, Tierney E, Thapa S, Ta HM, Burton L, Binning JM, Jacobson MP, Gross JD
• Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay.
  Nature structural & molecular biology 2018 Mugridge JS, Coller J, Gross JD
• Decapping enzymes STOP "cancer" ribosomes in their tracks.
  The EMBO journal 2018 Mugridge JS, Gross JD
• A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability.
  Cell host & microbe 2018 Nayak A, Kim DY, Trnka MJ, Kerr CH, Lidsky PV, Stanley DJ, Rivera BM, Li KH, Burlingame AL, Jan E, Frydman J, Gross JD, Andino R
• CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.
  The EMBO journal 2018 Chen SH, Jang GM, Hüttenhain R, Gordon DE, Du D, Newton BW, Johnson JR, Hiatt J, Hultquist JF, Johnson TL, Liu YL, Burton LA, Ye J, Reichermeier KM, Stroud RM, Marson A, Debnath J, Gross JD, Krogan NJ
• Control of mRNA decapping by autoinhibition.
  Nucleic acids research 2018 Paquette DR, Tibble RW, Daifuku TS, Gross JD
• Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis.
  Nature communications 2018 Mugridge JS, Tibble RW, Ziemniak M, Jemielity J, Gross JD
• Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.
  PLoS pathogens 2018 Binning JM, Smith AM, Hultquist JF, Craik CS, Caretta Cartozo N, Campbell MG, Burton L, La Greca F, McGregor MJ, Ta HM, Bartholomeeusen K, Peterlin BM, Krogan NJ, Sevillano N, Cheng Y, Gross JD
• Application of a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme for transcription start site mapping
  RNA 2018 DR Paquette, JS Mugridge, DE Weinberg, and JD Gross
• Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription.
  Annual review of virology 2017 Faust TB, Binning JM, Gross JD, Frankel AD
• Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2.
  Journal of molecular biology 2017 Isaac RS, Sanulli S, Tibble R, Hornsby M, Ravalin M, Craik CS, Gross JD, Narlikar GJ
• Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler.
  Science (New York, N.Y.) 2017 Sinha KK, Gross JD, Narlikar GJ
• CBFß and HIV Infection.
  Advances in experimental medicine and biology 2017 Kim DY, Gross JD
• Molecular biology: Messenger RNAs marked for longer life.
  Nature 2016 Weinberg DE, Gross JD
• Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
  Nature structural & molecular biology 2016 Mugridge JS, Ziemniak M, Jemielity J, Gross JD
• Two-headed tetraphosphate cap analogs are inhibitors of the Dcp1/2 RNA decapping complex.
  RNA (New York, N.Y.) 2016 Ziemniak M, Mugridge JS, Kowalska J, Rhoads RE, Gross JD, Jemielity J
• Thermodynamics of Rev-RNA interactions in HIV-1 Rev-RRE assembly.
  Biochemistry 2015 Jayaraman B, Mavor D, Gross JD, Frankel AD
• Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity.
  Cell reports 2015 Kane JR, Stanley DJ, Hultquist JF, Johnson JR, Mietrach N, Binning JM, Jónsson SR, Barelier S, Newton BW, Johnson TL, Franks-Skiba KE, Li M, Brown WL, Gunnarsson HI, Adalbjornsdóttir A, Fraser JS, …
• A mutually assured destruction mechanism attenuates light signaling in Arabidopsis.
  Science (New York, N.Y.) 2014 Ni W, Xu SL, Tepperman JM, Stanley DJ, Maltby DA, Gross JD, Burlingame AL, Wang ZY, Quail PH
• Active site conformational dynamics are coupled to catalysis in the mRNA decapping enzyme Dcp2.
  Structure (London, England : 1993) 2013 Aglietti RA, Floor SN, McClendon CL, Jacobson MP, Gross JD
• The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals.
  Nature structural & molecular biology 2013 Watson LC, Kuchenbecker KM, Schiller BJ, Gross JD, Pufall MA, Yamamoto KR
• Judge, jury, and executioner: DXO functions as a decapping enzyme and exoribonuclease in pre-mRNA quality control.
  Molecular cell 2013 Mugridge JS, Gross JD
• From systems to structure: bridging networks and mechanism.
  Molecular cell 2013 Fraser JS, Gross JD, Krogan NJ
• CBFβ stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression.
  Molecular cell 2013 Kim DY, Kwon E, Hartley PD, Crosby DC, Mann S, Krogan NJ, Gross JD
• Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.
  PLoS pathogens 2012 Stanley DJ, Bartholomeeusen K, Crosby DC, Kim DY, Kwon E, Yen L, Cartozo NC, Li M, Jäger S, Mason-Herr J, Hayashi F, Yokoyama S, Krogan NJ, Harris RS, Peterlin BM, Gross JD
• In support of the BMRB.
  Nature structural & molecular biology 2012 Markley JL, Akutsu H, Asakura T, Baldus M, Boelens R, Bonvin A, Kaptein R, Bax A, Bezsonova I, Gryk MR, Hoch JC, Korzhnev DM, Maciejewski MW, Case D, Chazin WJ, Cross TA, Dames S, Kessler H, Lange O, …
• The crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA.
  Protein science : a publication of the Protein Society 2012 Kwon E, Kim DY, Ngo TD, Gross CA, Gross JD, Kim KK
• Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan.
  Proceedings of the National Academy of Sciences of the United States of America 2012 Floor SN, Borja MS, Gross JD
• Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection.
  Nature 2011 Jäger S, Kim DY, Hultquist JF, Shindo K, LaRue RS, Kwon E, Li M, Anderson BD, Yen L, Stanley D, Mahon C, Kane J, Franks-Skiba K, Cimermancic P, Burlingame A, Sali A, Craik CS, Harris RS, Gross JD, …
• Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition.
  RNA (New York, N.Y.) 2010 Borja MS, Piotukh K, Freund C, Gross JD
• The crystal structure Escherichia coli Spy.
  Protein science : a publication of the Protein Society 2010 Kwon E, Kim DY, Gross CA, Gross JD, Kim KK
• A split active site couples cap recognition by Dcp2 to activation.
  Nature structural & molecular biology 2010 Floor SN, Jones BN, Hernandez GA, Gross JD
• Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.
  Nature structural & molecular biology 2010 Nayak A, Berry B, Tassetto M, Kunitomi M, Acevedo A, Deng C, Krutchinsky A, Gross J, Antoniewski C, Andino R
• Identification and analysis of the interaction between Edc3 and Dcp2 in Saccharomyces cerevisiae.
  Molecular and cellular biology 2010 Harigaya Y, Jones BN, Muhlrad D, Gross JD, Parker R
• An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model.
  Journal of molecular biology 2009 Harjes E, Gross PJ, Chen KM, Lu Y, Shindo K, Nowarski R, Gross JD, Kotler M, Harris RS, Matsuo H
• Ligand-induced conformational heterogeneity of cytochrome P450 CYP119 identified by 2D NMR spectroscopy with the unnatural amino acid (13)C-p-methoxyphenylalanine.
  Journal of the American Chemical Society 2008 Lampe JN, Floor SN, Gross JD, Nishida CR, Jiang Y, Trnka MJ, Ortiz de Montellano PR
• Control of mRNA decapping by Dcp2: An open and shut case?
  RNA biology 2008 Floor SN, Jones BN, Gross JD
• Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).
  Molecular and cellular biology 2008 Campbell LA, Faivre EJ, Show MD, Ingraham JG, Flinders J, Gross JD, Ingraham HA
• SRP RNA controls a conformational switch regulating the SRP-SRP receptor interaction.
  Nature structural & molecular biology 2008 Neher SB, Bradshaw N, Floor SN, Gross JD, Walter P
• mRNA decapping is promoted by an RNA-binding channel in Dcp2.
  Molecular cell 2008 Deshmukh MV, Jones BN, Quang-Dang DU, Flinders J, Floor SN, Kim C, Jemielity J, Kalek M, Darzynkiewicz E, Gross JD
• A kinetic assay to monitor RNA decapping under single- turnover conditions.
  Methods in enzymology 2008 Jones BN, Quang-Dang DU, Oku Y, Gross JD
• The structural basis of yeast prion strain variants.
  Nature 2007 Toyama BH, Kelly MJ, Gross JD, Weissman JS
• Backbone and sidechain methyl Ile (delta1), Leu and Val resonance assignments of the catalytic domain of the yeast mRNA decapping enzyme, Dcp2.
  Biomolecular NMR assignments 2007 Deshmukh MV, Oku Y, Gross JD
• Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G.
  Cell 2007 Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, Halperin JA, Wagner G
• Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.
  Journal of molecular biology 2005 von der Haar T, Oku Y, Ptushkina M, Moerke N, Wagner G, Gross JD, McCarthy JE
• A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.
  Molecular cell 2005 He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dötsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL
• NMR structure of the flavin domain from soluble methane monooxygenase reductase from Methylococcus capsulatus (Bath).
  Biochemistry 2004 Chatwood LL, Müller J, Gross JD, Wagner G, Lippard SJ
• The mRNA cap-binding protein eIF4E in post-transcriptional gene expression.
  Nature structural & molecular biology 2004 von der Haar T, Gross JD, Wagner G, McCarthy JE
• Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E.
  Cell 2003 Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G
• Broadband 13C-13C adiabatic mixing in solution optimized for high fields.
  Journal of magnetic resonance (San Diego, Calif. : 1997) 2003 Bennett AE, Gross JD, Wagner G
• A sensitive and robust method for obtaining intermolecular NOEs between side chains in large protein complexes.
  Journal of biomolecular NMR 2003 Gross JD, Gelev VM, Wagner G
• A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors.
  Journal of the American Chemical Society 2002 Lugovskoy AA, Degterev AI, Fahmy AF, Zhou P, Gross JD, Yuan J, Wagner G
• Global Fold Determination of large proteins using site-directed spin labeling
  Protein NMR for the Millenium 2002 JL Battiste, JD Gross, and G Wagner
• Interactions of the eukaryotic translation initiation factor eIF4E.
  Cold Spring Harbor symposia on quantitative biology 2001 Gross JD, Matsuo H, Fletcher M, Sachs AB, Wagner G
• The Cap-binding protein eIF4E promotes folding of a functional domain of yeast translation initiation factor eIF4G1.
  The Journal of biological chemistry 1999 Hershey PE, McWhirter SM, Gross JD, Wagner G, Alber T, Sachs AB
• Determination of the peptide torsion angle phi by 15N chemical shift and 13Calpha-1Halpha dipolar tensor correlation in solid-state MAS NMR.
  Journal of magnetic resonance (San Diego, Calif. : 1997) 1998 Hong M, Gross JD, Hu W, Griffin RG
• Effects of membrane peptide dynamics on high-resolution magic-angle spinning NMR
  Journal de Chimie Physique et de Physico-Chimie Biologique 1998 DE Warschawski, JD Gross, and RG Griffin
• Tilted n-fold symmetric radio frequency pulse sequences: Applications to CSA and heteronuclear dipolar recoupling in homonuclear dipolar coupled spin networks
  The Journal of Chemical Physics 1998 JD Gross, PR Costa, and RG Griffin
• Coupling amplification in 2D MAS NMR and its application to torsion angle determination in peptides.
  Journal of magnetic resonance (San Diego, Calif. : 1997) 1997 Hong M, Gross JD, Rienstra CM, Griffin RG, Kumashiro KK, Schmidt-Rohr K
• Dipolar recoupling in MAS NMR: a probe for segmental order in lipid bilayers
  Journal of the American Chemical Society 1997 JD Gross, DE Warschawski, and RG Griffin
• Site-Resolved Determination of Peptide Torsion Angle phi from the relative orientation of backbone NH and CH bonds by solid-state NMR
  The Journal of Physical Chemistry B 1997 M Hong, JD Gross, and RG Griffin
• Solid-state NMR measurement of psi in peptides: a NCCN 2Q-heteronuclear local field experiment
  Chemical Physics Letters 1997 PR Costa, JD Gross, M Hong, and RG Griffin
• Multidimensional NMR in lipid systems. Coherence transfer through J couplings under MAS
  Journal of Magnetic Resonance Series B 1995 JD Gross, PR Costa, JP Dubacq, DE Warschawski, PN Lirsac, PF Devaux, and RG Griffin
• Structural studies of a family of high affinity ligands for GPIIb/IIIa
  Journal of the American Chemical Society 1994 AC Bach, CJ Eyermann, JD Gross, MJ Bower, RL Harlow, PC Weber, WF DeGrado