UCSF

John Gross, PhD

Professor
Department of Pharmaceutical Chemistry
Gross
jd[email protected]
Phone: +1 415 502-1897
Fax: +1 415 502-8298
600 16th St, Rm S512E
UCSF Box 2280
San Francisco, CA 94158
United States

Links

Gross Lab
UCSF Profiles

Educational programs

UCSF centers, institutes, and research programs

What I do

I am interested in protein structure and dynamics related to gene expression. We study changes in protein structure that occur on time scales ranging from millions of years to a millionth of a second, with a focus on basic questions of how viruses cross-species and give rise to modern pandemics or how enzyme function is fine-tuned by cellular cues. Research in this area guides development of therapeutics for infectious disease and cancer.

Departmental research area

physical biology

My research expertise

NMR spectroscopy, structural biology, enzymology

Degrees

PhD, Physical Chemistry, Massachusetts Institute of Technology (MIT), 1998
BS, Chemistry, Sewanee: The University of the South, 1992

Biography

We investigate molecular machines that coordinate gene expression or antiviral immunity. Research areas include : i- RNA decay enzymes that act in mRNA quality control and gene regulatory pathways, and ii- nucleic acid based immune systems that protect animals from viruses and neutralization of these systems by viral accessory proteins. 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.

Research keywords

RNA Caps, Core Binding Factor beta Subunit, vif Gene Products, Human Immunodeficiency Virus, RNA, Fungal, Eukaryotic Initiation Factor-4E, Schizosaccharomyces, RNA, Messenger, RNA Stability, Cullin Proteins, Gene Products, vif, Cytosine Deaminase, Catalytic Domain, Cytidine Deaminase, Schizosaccharomyces pombe Proteins, Endoribonucleases

Publications

Lobel JH, Gross JD. Pat1 increases the range of decay factors and RNA bound by the Lsm1-7 complex. RNA. 2020 Jun 08.
Sanulli S, Gross JD, Narlikar GJ. Biophysical Properties of HP1-Mediated Heterochromatin. Cold Spring Harb Symp Quant Biol. 2020 Jun 03.
Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Apr 30.
Binning JM, Chesarino NM, Emerman M, Gross JD. Structural Basis for a Species-Specific Determinant of an SIV Vif Protein toward Hominid APOBEC3G Antagonism. Cell Host Microbe. 2019 12 11; 26(6):739-747.e4.
Lobel JH, Tibble RW, Gross JD. Pat1 activates late steps in mRNA decay by multiple mechanisms. Proc Natl Acad Sci U S A. 2019 11 19; 116(47):23512-23517.
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. ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection. Cell Host Microbe. 2019 07 10; 26(1):86-99.e7.
Ball KA, Chan LM, Stanley DJ, Tierney E, Thapa S, Ta HM, Burton L, Binning JM, Jacobson MP, Gross JD. Conformational Dynamics of the HIV-Vif Protein Complex. Biophys J. 2019 04 23; 116(8):1432-1445.
Mugridge JS, Coller J, Gross JD. Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay. Nat Struct Mol Biol. 2018 12; 25(12):1077-1085.
Mugridge JS, Gross JD. Decapping enzymes STOP "cancer" ribosomes in their tracks. EMBO J. 2018 12 03; 37(23).
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. A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability. Cell Host Microbe. 2018 10 10; 24(4):542-557.e9.
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. CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling. EMBO J. 2018 09 14; 37(18).
Paquette DR, Tibble RW, Daifuku TS, Gross JD. Control of mRNA decapping by autoinhibition. Nucleic Acids Res. 2018 07 06; 46(12):6318-6329.
Mugridge JS, Tibble RW, Ziemniak M, Jemielity J, Gross JD. Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis. Nat Commun. 2018 03 20; 9(1):1152.
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. Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors. PLoS Pathog. 2018 01; 14(1):e1006830.
DR Paquette, JS Mugridge, DE Weinberg, and JD Gross. Application of a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme for transcription start site mapping. RNA. 2018; 24(2):251-257.
Faust TB, Binning JM, Gross JD, Frankel AD. Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription. Annu Rev Virol. 2017 09 29; 4(1):241-260.
Isaac RS, Sanulli S, Tibble R, Hornsby M, Ravalin M, Craik CS, Gross JD, Narlikar GJ. Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2. J Mol Biol. 2017 11 24; 429(23):3666-3677.
Sinha KK, Gross JD, Narlikar GJ. Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler. Science. 2017 01 20; 355(6322).
Kim DY, Gross JD. CBFß and HIV Infection. Adv Exp Med Biol. 2017; 962:415-431.
Weinberg DE, Gross JD. Molecular biology: Messenger RNAs marked for longer life. Nature. 2017 01 19; 541(7637):293-294.
Mugridge JS, Ziemniak M, Jemielity J, Gross JD. Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nat Struct Mol Biol. 2016 Nov; 23(11):987-994.
Ziemniak M, Mugridge JS, Kowalska J, Rhoads RE, Gross JD, Jemielity J. Two-headed tetraphosphate cap analogs are inhibitors of the Dcp1/2 RNA decapping complex. RNA. 2016 Apr; 22(4):518-29.
Jayaraman B, Mavor D, Gross JD, Frankel AD. Thermodynamics of Rev-RNA interactions in HIV-1 Rev-RRE assembly. Biochemistry. 2015 Oct 27; 54(42):6545-54.
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, Harris RS, Andrésdóttir V, Gross JD, Krogan NJ. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity. Cell Rep. 2015 May 26; 11(8):1236-50.
Ni W, Xu SL, Tepperman JM, Stanley DJ, Maltby DA, Gross JD, Burlingame AL, Wang ZY, Quail PH. A mutually assured destruction mechanism attenuates light signaling in Arabidopsis. Science. 2014 Jun 06; 344(6188):1160-1164.
Aglietti RA, Floor SN, McClendon CL, Jacobson MP, Gross JD. Active site conformational dynamics are coupled to catalysis in the mRNA decapping enzyme Dcp2. Structure. 2013 Sep 03; 21(9):1571-80.
Watson LC, Kuchenbecker KM, Schiller BJ, Gross JD, Pufall MA, Yamamoto KR. The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals. Nat Struct Mol Biol. 2013 Jul; 20(7):876-83.
Mugridge JS, Gross JD. Judge, jury, and executioner: DXO functions as a decapping enzyme and exoribonuclease in pre-mRNA quality control. Mol Cell. 2013 Apr 11; 50(1):2-4.
Fraser JS, Gross JD, Krogan NJ. From systems to structure: bridging networks and mechanism. Mol Cell. 2013 Jan 24; 49(2):222-31.
Kim DY, Kwon E, Hartley PD, Crosby DC, Mann S, Krogan NJ, Gross JD. CBFß stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression. Mol Cell. 2013 Feb 21; 49(4):632-44.
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. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G. PLoS Pathog. 2012 Dec; 8(12):e1003085.
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, Madl T, Reif B, Sattler M, Eliezer D, Fersht A, Forman-Kay J, Kay LE, Fraser J, Gross J, Kortemme T, Sali A, Fujiwara T, Gardner K, Luo X, Rizo-Rey J, Rosen M, Gil RR, Ho C, Rule G, Gronenborn AM, Ishima R, Klein-Seetharaman J, Tang P, van der Wel P, Xu Y, Grzesiek S, Hiller S, Seelig J, Laue ED, Mott H, Nietlispach D, Barsukov I, Lian LY, Middleton D, Blumenschein T, Moore G, Campbell I, Schnell J, Vakonakis IJ, Watts A, Conte MR, Mason J, Pfuhl M, Sanderson MR, Craven J, Williamson M, Dominguez C, Roberts G, Günther U, Overduin M, Werner J, Williamson P, Blindauer C, Crump M, Driscoll P, Frenkiel T, Golovanov A, Matthews S, Parkinson J, Uhrin D, Williams M, Neuhaus D, Oschkinat H, Ramos A, Shaw DE, Steinbeck C, Vendruscolo M, Vuister GW, Walters KJ, Weinstein H, Wüthrich K, Yokoyama S. In support of the BMRB. Nat Struct Mol Biol. 2012 Sep; 19(9):854-60.
Kwon E, Kim DY, Ngo TD, Gross CA, Gross JD, Kim KK. The crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA. Protein Sci. 2012 Sep; 21(9):1334-43.
Floor SN, Borja MS, Gross JD. Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2872-7.
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, Krogan NJ. Vif hijacks CBF-ß to degrade APOBEC3G and promote HIV-1 infection. Nature. 2011 Dec 21; 481(7381):371-5.
Borja MS, Piotukh K, Freund C, Gross JD. Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition. RNA. 2011 Feb; 17(2):278-90.
Kwon E, Kim DY, Gross CA, Gross JD, Kim KK. The crystal structure Escherichia coli Spy. Protein Sci. 2010 Nov; 19(11):2252-9.
Floor SN, Jones BN, Hernandez GA, Gross JD. A split active site couples cap recognition by Dcp2 to activation. Nat Struct Mol Biol. 2010 Sep; 17(9):1096-101.
Nayak A, Berry B, Tassetto M, Kunitomi M, Acevedo A, Deng C, Krutchinsky A, Gross J, Antoniewski C, Andino R. Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila. Nat Struct Mol Biol. 2010 May; 17(5):547-54.
Harigaya Y, Jones BN, Muhlrad D, Gross JD, Parker R. Identification and analysis of the interaction between Edc3 and Dcp2 in Saccharomyces cerevisiae. Mol Cell Biol. 2010 Mar; 30(6):1446-56.
Harjes E, Gross PJ, Chen KM, Lu Y, Shindo K, Nowarski R, Gross JD, Kotler M, Harris RS, Matsuo H. An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model. J Mol Biol. 2009 Jun 26; 389(5):819-32.
Lampe JN, Floor SN, Gross JD, Nishida CR, Jiang Y, Trnka MJ, Ortiz de Montellano PR. Ligand-induced conformational heterogeneity of cytochrome P450 CYP119 identified by 2D NMR spectroscopy with the unnatural amino acid (13)C-p-methoxyphenylalanine. J Am Chem Soc. 2008 Dec 03; 130(48):16168-9.
Floor SN, Jones BN, Gross JD. Control of mRNA decapping by Dcp2: An open and shut case? RNA Biol. 2008 Oct-Dec; 5(4):189-92.
Campbell LA, Faivre EJ, Show MD, Ingraham JG, Flinders J, Gross JD, Ingraham HA. Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1). Mol Cell Biol. 2008 Dec; 28(24):7476-86.
Neher SB, Bradshaw N, Floor SN, Gross JD, Walter P. SRP RNA controls a conformational switch regulating the SRP-SRP receptor interaction. Nat Struct Mol Biol. 2008 Sep; 15(9):916-23.
Deshmukh MV, Jones BN, Quang-Dang DU, Flinders J, Floor SN, Kim C, Jemielity J, Kalek M, Darzynkiewicz E, Gross JD. mRNA decapping is promoted by an RNA-binding channel in Dcp2. Mol Cell. 2008 Feb 15; 29(3):324-36.
Jones BN, Quang-Dang DU, Oku Y, Gross JD. A kinetic assay to monitor RNA decapping under single- turnover conditions. Methods Enzymol. 2008; 448:23-40.
Toyama BH, Kelly MJ, Gross JD, Weissman JS. The structural basis of yeast prion strain variants. Nature. 2007 Sep 13; 449(7159):233-7.
Deshmukh MV, Oku Y, Gross JD. Backbone and sidechain methyl Ile (delta1), Leu and Val resonance assignments of the catalytic domain of the yeast mRNA decapping enzyme, Dcp2. Biomol NMR Assign. 2007 Jul; 1(1):17-8.
Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, Halperin JA, Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007 Jan 26; 128(2):257-67.
von der Haar T, Oku Y, Ptushkina M, Moerke N, Wagner G, Gross JD, McCarthy JE. Folding transitions during assembly of the eukaryotic mRNA cap-binding complex. J Mol Biol. 2006 Mar 03; 356(4):982-92.
He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dötsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL. A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada. Mol Cell. 2005 Oct 07; 20(1):117-29.
Chatwood LL, Müller J, Gross JD, Wagner G, Lippard SJ. NMR structure of the flavin domain from soluble methane monooxygenase reductase from Methylococcus capsulatus (Bath). Biochemistry. 2004 Sep 28; 43(38):11983-91.
von der Haar T, Gross JD, Wagner G, McCarthy JE. The mRNA cap-binding protein eIF4E in post-transcriptional gene expression. Nat Struct Mol Biol. 2004 Jun; 11(6):503-11.
Gross JD, Moerke NJ, von der Haar T, Lugovskoy AA, Sachs AB, McCarthy JE, Wagner G. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell. 2003 Dec 12; 115(6):739-50.
Bennett AE, Gross JD, Wagner G. Broadband 13C-13C adiabatic mixing in solution optimized for high fields. J Magn Reson. 2003 Nov; 165(1):59-79.
Gross JD, Gelev VM, Wagner G. A sensitive and robust method for obtaining intermolecular NOEs between side chains in large protein complexes. J Biomol NMR. 2003 Mar; 25(3):235-42.
Lugovskoy AA, Degterev AI, Fahmy AF, Zhou P, Gross JD, Yuan J, Wagner G. A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc. 2002 Feb 20; 124(7):1234-40.
JL Battiste, JD Gross, and G Wagner. Global Fold Determination of large proteins using site-directed spin labeling. Protein NMR for the Millenium. 2002; 79-101.
Gross JD, Matsuo H, Fletcher M, Sachs AB, Wagner G. Interactions of the eukaryotic translation initiation factor eIF4E. Cold Spring Harb Symp Quant Biol. 2001; 66:397-402.
Hershey PE, McWhirter SM, Gross JD, Wagner G, Alber T, Sachs AB. The Cap-binding protein eIF4E promotes folding of a functional domain of yeast translation initiation factor eIF4G1. J Biol Chem. 1999 Jul 23; 274(30):21297-304.
Hong M, Gross JD, Hu W, Griffin RG. Determination of the peptide torsion angle phi by 15N chemical shift and 13Calpha-1Halpha dipolar tensor correlation in solid-state MAS NMR. J Magn Reson. 1998 Nov; 135(1):169-77.
DE Warschawski, JD Gross, and RG Griffin. Effects of membrane peptide dynamics on high-resolution magic-angle spinning NMR. Journal de Chimie Physique et de Physico-Chimie Biologique. 1998; 95(2):460-466.
JD Gross, PR Costa, 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; 108(17):7286-7293.
Hong M, Gross JD, Rienstra CM, Griffin RG, Kumashiro KK, Schmidt-Rohr K. Coupling amplification in 2D MAS NMR and its application to torsion angle determination in peptides. J Magn Reson. 1997 Nov; 129(1):85-92.
JD Gross, DE Warschawski, and RG Griffin. Dipolar recoupling in MAS NMR: a probe for segmental order in lipid bilayers. Journal of the American Chemical Society. 1997; 119(4):796-802.
M Hong, JD Gross, 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; 101(30):5869-5874.
PR Costa, JD Gross, M Hong, and RG Griffin. Solid-state NMR measurement of psi in peptides: a NCCN 2Q-heteronuclear local field experiment. Chemical Physics Letters. 1997; 280(1-2):95-103.
JD Gross, PR Costa, JP Dubacq, DE Warschawski, PN Lirsac, PF Devaux, and RG Griffin. Multidimensional NMR in lipid systems. Coherence transfer through J couplings under MAS. Journal of Magnetic Resonance Series B. 1995; 106:190.
AC Bach, CJ Eyermann, JD Gross, MJ Bower, RL Harlow, PC Weber, WF DeGrado. Structural studies of a family of high affinity ligands for GPIIb/IIIa. Journal of the American Chemical Society. 1994; 116(8):3207-3219.
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