Robert Stroud, MA, PhD

Professor
Biochemistry and BIophysics
+1 415 476-4224

We seek to understand molecular mechanisms of certain key biological processes, as well as signal transduction between processes at the level of protein structure, dynamics, and mechanism. Molecular cloning, expression, site-directed mutagenesis, and strong focus onto biochemistry are a key part of the arsenal for defining molecular mechanisms. We focus on the questions of how signals cross membranes, and how membrane proteins and membrane channels work at the level of atomic structure. We also focus on how the signal recognition particle (SRP) directs membrane and secreted proteins to the membrane.

Publications: 

Structural basis for activation of voltage sensor domains in an ion channel TPC1.

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

Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM

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

Crystal Structure of a ligand-bound LacY-Nanobody Complex.

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

Kumar H, Finer-Moore JS, Jiang X, Smirnova I, Kasho V, Pardon E, Steyaert J, Kaback HR, Stroud RM

On the structure and mechanism of two-pore channels.

The FEBS journal

Kintzer AF, Stroud RM

Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP.

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

Nöll A, Thomas C, Herbring V, Zollmann T, Barth K, Mehdipour AR, Tomasiak TM, Brüchert S, Joseph B, Abele R, Oliéric V, Wang M, Diederichs K, Hummer G, Stroud RM, Pos KM, Tampé R

The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical.

Structure (London, England : 1993)

Galilee M, Britan-Rosich E, Griner SL, Uysal S, Baumgärtel V, Lamb DC, Kossiakoff AA, Kotler M, Stroud RM, Marx A, Alian A

Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers.

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

Thurtle-Schmidt BH, Stroud RM

Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides.

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

Kapoor K, Finer-Moore JS, Pedersen BP, Caboni L, Waight A, Hillig RC, Bringmann P, Heisler I, Müller T, Siebeneicher H, Stroud RM

Integral Membrane Protein Expression in Saccharomyces cerevisiae.

Methods in molecular biology (Clifton, N.J.)

Boswell-Casteel RC, Johnson JM, Stroud RM, Hays FA

Small-Scale Screening to Large-Scale Over-Expression of Human Membrane Proteins for Structural Studies.

Methods in molecular biology (Clifton, N.J.)

Chaudhary S, Saha S, Thamminana S, Stroud RM

Fungal association and utilization of phosphate by plants: success, limitations, and future prospects.

Frontiers in microbiology

Johri AK, Oelmüller R, Dua M, Yadav V, Kumar M, Tuteja N, Varma A, Bonfante P, Persson BL, Stroud RM

Structure of LacY with an a-substituted galactoside: Connecting the binding site to the protonation site.

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

Kumar H, Finer-Moore JS, Kaback HR, Stroud RM

Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion.

Cell

Rosenberg OS, Dovala D, Li X, Connolly L, Bendebury A, Finer-Moore J, Holton J, Cheng Y, Stroud RM, Cox JS

Hotspots in an obligate homodimeric anticancer target. Structural and functional effects of interfacial mutations in human thymidylate synthase.

Journal of medicinal chemistry

Salo-Ahen OM, Tochowicz A, Pozzi C, Cardinale D, Ferrari S, Boum Y, Mangani S, Stroud RM, Saxena P, Myllykallio H, Costi MP, Ponterini G, Wade RC

Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.

Journal of medicinal chemistry

Tochowicz A, Santucci M, Saxena P, Guaitoli G, Trande M, Finer-Moore J, Stroud RM, Costi MP

Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter.

Nature

Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB, Stiller SB, Robles-Colmanares Y, Stroud RM, Tampé R, Craik CS, Cheng Y

General qPCR and Plate Reader Methods for Rapid Optimization of Membrane Protein Purification and Crystallization Using Thermostability Assays.

Current protocols in protein science

Tomasiak TM, Pedersen BP, Chaudhary S, Rodriguez A, Colmanares YR, Roe-Zurz Z, Thamminana S, Tessema M, Stroud RM

Tetra detector analysis of membrane proteins.

Current protocols in protein science

Miercke LJ, Robbins RA, Stroud RM

Structure of a new DNA-binding domain which regulates pathogenesis in a wide variety of fungi.

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

Lohse MB, Rosenberg OS, Cox JS, Stroud RM, Finer-Moore JS, Johnson AD

Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.

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

Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM

Structure of sugar-bound LacY.

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

Kumar H, Kasho V, Smirnova I, Finer-Moore JS, Kaback HR, Stroud RM

Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter.

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

Pak JE, Ekendé EN, Kifle EG, O'Connell JD, De Angelis F, Tessema MB, Derfoufi KM, Robles-Colmenares Y, Robbins RA, Goormaghtigh E, Vandenbussche G, Stroud RM

Structural basis for alternating access of a eukaryotic calcium/proton exchanger.

Nature

Waight AB, Pedersen BP, Schlessinger A, Bonomi M, Chau BH, Roe-Zurz Z, Risenmay AJ, Sali A, Stroud RM

Mg2+ binds to the surface of thymidylate synthase and affects hydride transfer at the interior active site.

Journal of the American Chemical Society

Wang Z, Sapienza PJ, Abeysinghe T, Luzum C, Lee AL, Finer-Moore JS, Stroud RM, Kohen A

Crystal structure of a eukaryotic phosphate transporter.

Nature

Pedersen BP, Kumar H, Waight AB, Risenmay AJ, Roe-Zurz Z, Chau BH, Schlessinger A, Bonomi M, Harries W, Sali A, Johri AK, Stroud RM

Coordinating the impact of structural genomics on the human a-helical transmembrane proteome.

Nature structural & molecular biology

Pieper U, Schlessinger A, Kloppmann E, Chang GA, Chou JJ, Dumont ME, Fox BG, Fromme P, Hendrickson WA, Malkowski MG, Rees DC, Stokes DL, Stowell MH, Wiener MC, Rost B, Stroud RM, Stevens RC, Sali A

Inhibitor of ovarian cancer cells growth by virtual screening: a new thiazole derivative targeting human thymidylate synthase.

Journal of medicinal chemistry

Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP

A remote mutation affects the hydride transfer by disrupting concerted protein motions in thymidylate synthase.

Journal of the American Chemical Society

Wang Z, Abeysinghe T, Finer-Moore JS, Stroud RM, Kohen A

LpxI structures reveal how a lipid A precursor is synthesized.

Nature structural & molecular biology

Metzger LE, Lee JK, Finer-Moore JS, Raetz CR, Stroud RM

The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism.

Acta crystallographica. Section D, Biological crystallography

Pozzi C, Ferrari S, Cortesi D, Luciani R, Stroud RM, Catalano A, Costi MP, Mangani S

Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter.

Annals of neurology

Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM, Cree BA, Zamvil SS

Insights into the mechanism of bovine CD38/NAD+glycohydrolase from the X-ray structures of its Michaelis complex and covalently-trapped intermediates.

PloS one

Egea PF, Muller-Steffner H, Kuhn I, Cakir-Kiefer C, Oppenheimer NJ, Stroud RM, Kellenberger E, Schuber F

Fabs enable single particle cryoEM studies of small proteins.

Structure (London, England : 1993)

Wu S, Avila-Sakar A, Kim J, Booth DS, Greenberg CH, Rossi A, Liao M, Li X, Alian A, Griner SL, Juge N, Yu Y, Mergel CM, Chaparro-Riggers J, Strop P, Tampé R, Edwards RH, Stroud RM, Craik CS, Cheng Y

Overexpressing human membrane proteins in stably transfected and clonal human embryonic kidney 293S cells.

Nature protocols

Chaudhary S, Pak JE, Gruswitz F, Sharma V, Stroud RM

Rapid identification of recombinant Fabs that bind to membrane proteins.

Methods (San Diego, Calif.)

Kim J, Stroud RM, Craik CS

Efficient expression screening of human membrane proteins in transiently transfected Human Embryonic Kidney 293S cells.

Methods (San Diego, Calif.)

Chaudhary S, Pak JE, Pedersen BP, Bang LJ, Zhang LB, Ngaw SM, Green RG, Sharma V, Stroud RM

Membranes.

Current opinion in structural biology

Stroud RM, Schertler GF

EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a unique dimeric structure among helix-turn-helix proteins.

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

Rosenberg OS, Dovey C, Tempesta M, Robbins RA, Finer-Moore JS, Stroud RM, Cox JS

Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1.

BMC biology

Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P

Structural and functional basis for RNA cleavage by Ire1.

BMC biology

Korennykh AV, Korostelev AA, Egea PF, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P

New tools in membrane protein determination.

F1000 biology reports

Stroud RM

Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica.

PloS one

Nelson PA, Khodadoust M, Prodhomme T, Spencer C, Patarroyo JC, Varrin-Doyer M, Ho JD, Stroud RM, Zamvil SS

Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes.

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

Egea PF, Stroud RM

Structural context shapes the aquaporin selectivity filter.

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

Savage DF, O'Connell JD, Miercke LJ, Finer-Moore J, Stroud RM

Unlocking the eukaryotic membrane protein structural proteome.

Current opinion in structural biology

Lee JK, Stroud RM

Metal-induced conformational changes in ZneB suggest an active role of membrane fusion proteins in efflux resistance systems.

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

De Angelis F, Lee JK, O'Connell JD, Miercke LJ, Verschueren KH, Srinivasan V, Bauvois C, Govaerts C, Robbins RA, Ruysschaert JM, Stroud RM, Vandenbussche G

Function of human Rh based on structure of RhCG at 2.1 A.

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

Gruswitz F, Chaudhary S, Ho JD, Schlessinger A, Pezeshki B, Ho CM, Sali A, Westhoff CM, Stroud RM

Comparison of human solute carriers.

Protein science : a publication of the Protein Society

Schlessinger A, Matsson P, Shima JE, Pieper U, Yee SW, Kelly L, Apeltsin L, Stroud RM, Ferrin TE, Giacomini KM, Sali A

Overexpression and purification of integral membrane proteins in yeast.

Methods in enzymology

Hays FA, Roe-Zurz Z, Stroud RM

A survey of integral alpha-helical membrane proteins.

Journal of structural and functional genomics

Kelly L, Pieper U, Eswar N, Hays FA, Li M, Roe-Zurz Z, Kroetz DL, Giacomini KM, Stroud RM, Sali A

Catalytically-active complex of HIV-1 integrase with a viral DNA substrate binds anti-integrase drugs.

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

Alian A, Griner SL, Chiang V, Tsiang M, Jones G, Birkus G, Geleziunas R, Leavitt AD, Stroud RM

Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance.

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

Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE, Robbins RA, Miercke LJ, Stroud RM

Crystal structure of an RluF-RNA complex: a base-pair rearrangement is the key to selectivity of RluF for U2604 of the ribosome.

Journal of molecular biology

Alian A, DeGiovanni A, Griner SL, Finer-Moore JS, Stroud RM

2007 annual progress report synopsis of the Center for Structures of Membrane Proteins.

Journal of structural and functional genomics

Stroud RM, Choe S, Holton J, Kaback HR, Kwiatkowski W, Minor DL, Riek R, Sali A, Stahlberg H, Harries W

A general protocol for the crystallization of membrane proteins for X-ray structural investigation.

Nature protocols

Newby ZE, O'Connell JD, Gruswitz F, Hays FA, Harries WE, Harwood IM, Ho JD, Lee JK, Savage DF, Miercke LJ, Stroud RM

The unfolded protein response signals through high-order assembly of Ire1.

Nature

Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Zhang C, Shokat KM, Stroud RM, Walter P

Selecting optimum eukaryotic integral membrane proteins for structure determination by rapid expression and solubilization screening.

Journal of molecular biology

Li M, Hays FA, Roe-Zurz Z, Vuong L, Kelly L, Ho CM, Robbins RM, Pieper U, O'Connell JD, Miercke LJ, Giacomini KM, Sali A, Stroud RM

Ratiocinative screen of eukaryotic integral membrane protein expression and solubilization for structure determination.

Journal of structural and functional genomics

Hays FA, Roe-Zurz Z, Li M, Kelly L, Gruswitz F, Sali A, Stroud RM

Crystal structure of bovine mitochondrial factor B at 0.96-A resolution.

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

Lee JK, Belogrudov GI, Stroud RM

Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum.

Nature structural & molecular biology

Newby ZE, O'Connell J, Robles-Colmenares Y, Khademi S, Miercke LJ, Stroud RM

Structure of a TrmA-RNA complex: A consensus RNA fold contributes to substrate selectivity and catalysis in m5U methyltransferases.

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

Alian A, Lee TT, Griner SL, Stroud RM, Finer-Moore J

Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage.

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

Du Z, Lee JK, Tjhen R, Stroud RM, James TL

TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists.

Science (New York, N.Y.)

Menuz K, Stroud RM, Nicoll RA, Hays FA

Cell-free complements in vivo expression of the E. coli membrane proteome.

Protein science : a publication of the Protein Society

Savage DF, Anderson CL, Robles-Colmenares Y, Newby ZE, Stroud RM

Structural basis of aquaporin inhibition by mercury.

Journal of molecular biology

Savage DF, Stroud RM

The crystal structure of E. coli rRNA pseudouridine synthase RluE.

Journal of molecular biology

Pan H, Ho JD, Stroud RM, Finer-Moore J

Transmembrane transporters: an open and closed case.

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

Stroud RM

Inhibitory complex of the transmembrane ammonia channel, AmtB, and the cytosolic regulatory protein, GlnK, at 1.96 A.

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

Gruswitz F, O'Connell J, Stroud RM

The role of protein dynamics in thymidylate synthase catalysis: variants of conserved 2'-deoxyuridine 5'-monophosphate (dUMP)-binding Tyr-261.

Biochemistry

Newby Z, Lee TT, Morse RJ, Liu Y, Liu L, Venkatraman P, Santi DV, Finer-Moore JS, Stroud RM

On the mechanism of sensing unfolded protein in the endoplasmic reticulum.

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

Credle JJ, Finer-Moore JS, Papa FR, Stroud RM, Walter P

Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A.

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

Lee JK, Kozono D, Remis J, Kitagawa Y, Agre P, Stroud RM

The structure of Cryptococcus neoformans thymidylate synthase suggests strategies for using target dynamics for species-specific inhibition.

Acta crystallographica. Section D, Biological crystallography

Finer-Moore JS, Anderson AC, O'Neil RH, Costi MP, Ferrari S, Krucinski J, Stroud RM

Targeting proteins to membranes: structure of the signal recognition particle.

Current opinion in structural biology

Egea PF, Stroud RM, Walter P

De novo design of an IL-4 antagonist and its structure at 1.9 A.

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

Laporte SL, Forsyth CM, Cunningham BC, Miercke LJ, Akhavan D, Stroud RM

Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry.

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

Chu F, Shan SO, Moustakas DT, Alber F, Egea PF, Stroud RM, Walter P, Burlingame AL

The channel architecture of aquaporin 0 at a 2.2-A resolution.

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

Harries WE, Akhavan D, Miercke LJ, Khademi S, Stroud RM

Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 A.

Science (New York, N.Y.)

Khademi S, O'Connell J, Remis J, Robles-Colmenares Y, Miercke LJ, Stroud RM

An antibiotic factory caught in action.

Nature structural & molecular biology

Keatinge-Clay AT, Maltby DA, Medzihradszky KF, Khosla C, Stroud RM

Mechanistic diversity of cytokine receptor signaling across cell membranes.

Science's STKE : signal transduction knowledge environment

Stroud RM, Wells JA

Substrate twinning activates the signal recognition particle and its receptor.

Nature

Egea PF, Shan SO, Napetschnig J, Savage DF, Walter P, Stroud RM

Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z.

PLoS biology

Savage DF, Egea PF, Robles-Colmenares Y, O'Connell JD, Stroud RM

Water and glycerol permeation through the glycerol channel GlpF and the aquaporin family.

Journal of synchrotron radiation

Lee JK, Khademi S, Harries W, Savage D, Miercke L, Stroud RM

Selectivity and conductance among the glycerol and water conducting aquaporin family of channels.

FEBS letters

Stroud RM, Savage D, Miercke LJ, Lee JK, Khademi S, Harries W

Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fit.

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

Pan H, Agarwalla S, Moustakas DT, Finer-Moore J, Stroud RM

Glycerol facilitator GlpF and the associated aquaporin family of channels.

Current opinion in structural biology

Stroud RM, Miercke LJ, O'Connell J, Khademi S, Lee JK, Remis J, Harries W, Robles Y, Akhavan D

The structural roles of conserved Pro196, Pro197 and His199 in the mechanism of thymidylate synthase.

Protein engineering

Gonzalez-Pacanowska D, Ruiz-Perez LM, Carreras-Gómez MA, Costi MP, Stroud RM, Finer-Moore J, Santi DV

Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90.

Chemistry & biology

Jez JM, Chen JC, Rastelli G, Stroud RM, Santi DV

Structure of human pro-chymase: a model for the activating transition of granule-associated proteases.

Biochemistry

Reiling KK, Krucinski J, Miercke LJ, Raymond WW, Caughey GH, Stroud RM

Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase.

Structure (London, England : 1993)

Keatinge-Clay AT, Shelat AA, Savage DF, Tsai SC, Miercke LJ, O'Connell JD, Khosla C, Stroud RM

The glycerol facilitator GlpF its aquaporin family of channels, and their selectivity.

Advances in protein chemistry

Stroud RM, Nollert P, Miercke L

Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway.

Structure (London, England : 1993)

Pan H, Tsai Sc, Meadows ES, Miercke LJ, Keatinge-Clay AT, O'Connell J, Khosla C, Stroud RM

Structural basis for mobility in the 1.1 A crystal structure of the NG domain of Thermus aquaticus Ffh.

Journal of molecular biology

Ramirez UD, Minasov G, Focia PJ, Stroud RM, Walter P, Kuhn P, Freymann DM

Structure-based studies on species-specific inhibition of thymidylate synthase.

Biochimica et biophysica acta

Costi MP, Tondi D, Rinaldi M, Barlocco D, Pecorari P, Soragni F, Venturelli A, Stroud RM

Control of the selectivity of the aquaporin water channel family by global orientational tuning.

Science (New York, N.Y.)

Tajkhorshid E, Nollert P, Jensen MØ, Miercke LJ, O'Connell J, Stroud RM, Schulten K

Encoding Selectivity of a Transmembrane Channel.

TheScientificWorldJournal

Stroud RM, Nollert P, Miercke LJW, Harries WEC, O'Connell J

Characterization of the 23 S ribosomal RNA m5U1939 methyltransferase from Escherichia coli.

The Journal of biological chemistry

Agarwalla S, Kealey JT, Santi DV, Stroud RM

The structure of GlpF, a glycerol conducting channel.

Novartis Foundation symposium

Fu D, Libson A, Stroud R

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding.

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

Chen JC, Krucinski J, Miercke LJ, Finer-Moore JS, Tang AH, Leavitt AD, Stroud RM

Signal sequence recognition and protein targeting.

Current opinion in structural biology

Stroud RM, Walter P

Ion-channel-forming colicins.

Current opinion in structural biology

Stroud RM, Reiling K, Wiener M, Freymann D

Significance of structural changes in proteins: expected errors in refined protein structures.

Protein science : a publication of the Protein Society

Stroud RM, Fauman EB

Purification and crystallization of creatine kinase from rabbit skeletal muscle.

The Journal of biological chemistry

Hershenson S, Helmers N, Desmueles P, Stroud R