John Gross, PhD

Pharmaceutical Chemistry
+1 415 502-1897

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.


Pat1 activates late steps in mRNA decay by multiple mechanisms.

Proceedings of the National Academy of Sciences of the United States of America

Lobel JH, Tibble RW, Gross JD

ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.

Cell host & microbe

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

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

Mugridge JS, Coller J, Gross JD

Decapping enzymes STOP "cancer" ribosomes in their tracks.

The EMBO journal

Mugridge JS, Gross JD

A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability.

Cell host & microbe

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

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

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

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

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

Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2.

Journal of molecular biology

Isaac RS, Sanulli S, Tibble R, Hornsby M, Ravalin M, Craik CS, Gross JD, Narlikar GJ

CBFß and HIV Infection.

Advances in experimental medicine and biology

Kim DY, Gross JD

Structural basis of mRNA-cap recognition by Dcp1-Dcp2.

Nature structural & molecular biology

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.)

Ziemniak M, Mugridge JS, Kowalska J, Rhoads RE, Gross JD, Jemielity J

Thermodynamics of Rev-RNA interactions in HIV-1 Rev-RRE assembly.


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

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

A mutually assured destruction mechanism attenuates light signaling in Arabidopsis.

Science (New York, N.Y.)

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)

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

Watson LC, Kuchenbecker KM, Schiller BJ, Gross JD, Pufall MA, Yamamoto KR

From systems to structure: bridging networks and mechanism.

Molecular cell

Fraser JS, Gross JD, Krogan NJ

CBFß stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression.

Molecular cell

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

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

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

The crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA.

Protein science : a publication of the Protein Society

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

Floor SN, Borja MS, Gross JD

Vif hijacks CBF-ß to degrade APOBEC3G and promote HIV-1 infection.


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

Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition.

RNA (New York, N.Y.)

Borja MS, Piotukh K, Freund C, Gross JD

The crystal structure Escherichia coli Spy.

Protein science : a publication of the Protein Society

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

Floor SN, Jones BN, Hernandez GA, Gross JD

Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.

Nature structural & molecular biology

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

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

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

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

Floor SN, Jones BN, Gross JD

Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).

Molecular and cellular biology

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

Neher SB, Bradshaw N, Floor SN, Gross JD, Walter P

mRNA decapping is promoted by an RNA-binding channel in Dcp2.

Molecular cell

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

Jones BN, Quang-Dang DU, Oku Y, Gross JD

The structural basis of yeast prion strain variants.


Toyama BH, Kelly MJ, Gross JD, Weissman JS

Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G.


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

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

He C, Hus JC, Sun LJ, Zhou P, Norman DP, Dötsch V, Wei H, Gross JD, Lane WS, Wagner G, Verdine GL

The mRNA cap-binding protein eIF4E in post-transcriptional gene expression.

Nature structural & molecular biology

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.


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)

Bennett AE, Gross JD, 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

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

JL Battiste, JD Gross, and G Wagner

Interactions of the eukaryotic translation initiation factor eIF4E.

Cold Spring Harbor symposia on quantitative biology

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

Hershey PE, McWhirter SM, Gross JD, Wagner G, Alber T, Sachs AB

Effects of membrane peptide dynamics on high-resolution magic-angle spinning NMR

Journal de Chimie Physique et de Physico-Chimie Biologique

DE Warschawski, JD Gross, 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)

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

JD Gross, DE Warschawski, and RG Griffin

Solid-state NMR measurement of psi in peptides: a NCCN 2Q-heteronuclear local field experiment

Chemical Physics Letters

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

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

AC Bach, CJ Eyermann, JD Gross, MJ Bower, RL Harlow, PC Weber, WF DeGrado