John Gross, PhD
John Gross studies the molecular structure of human and viral proteins to understand how they interact, control cellular function, and cause disease. His lab combines a wide variety of molecular biology and quantitative biochemistry techniques with biophysics and structural biology experiments, such as NMR spectroscopy and X-ray crystallography, in order to understand how the composition, structure, and dynamics of multi-protein complexes affect their cellular function. His lab primarily focuses on RNA decay and host-virus protein interactions of HIV.
He co-leads the Vif projects on HARC as well as co-leading the X-ray structure core.
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.
- Binning JM, Smith AM, Hultquist JF, Craik CS, Caretta 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 Jan 05; 14(1):e1006830.
- 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.
- 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.
- 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.
- 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.
- 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.