The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions.

Nature structural & molecular biology

Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR


Stacked binding of a PET ligand to Alzheimer’s tau paired helical filaments.

Nature Communications

Merz GE, Chalkley MJ, Tan SK, Tse E, Lee J, Prusiner SB, Paras NA, DeGrado WF, Southworth DR


Chemical Features of Polyanions Modulate Tau Aggregation and Conformational States.

Journal of the American Chemical Society

Montgomery KM, Carroll EC, Thwin AC, Quddus AY, Hodges P, Southworth DR, Gestwicki JE



Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3.

Cell reports

Cupo RR, Rizo AN, Braun GA, Tse E, Chuang E, Gupta K, Southworth DR, Shorter J

Structural and mechanistic studies of Skd3 (human CLPB) provide insight into disease-causing mutations and reveal unique AAA+ oligomerization.

Biophysical Journal

Alexandrea Rizo, Ryan R. Cupo, James Shorter, Daniel R. Southworth

Structural basis for client engagement and chaperone cycling by human mitochondrial Hsp60.

Biophysical Journal

Julian R. Braxton, Jason E. Gestwicki, Daniel R. Southworth

Structural basis for recognition of the Hsp90 closed, ATP state by the TPR-containing co-chaperone FKBP51.

Alzheimer's & Dementia

Kanghyun Lee, Aye Thwin, Eric Tse, Stephanie Gates, Daniel Southworth

Assembly principles of the human R2TP chaperone complex reveal the presence of R2T and R2P complexes.

Structure (London, England : 1993)

Seraphim TV, Nano N, Cheung YWS, Aluksanasuwan S, Colleti C, Mao YQ, Bhandari V, Young G, Höll L, Phanse S, Gordiyenko Y, Southworth DR, Robinson CV, Thongboonkerd V, Gava LM, Borges JC, Babu M, Barbosa LRS, Ramos CHI, Kukura P, Houry WA


The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state

Molecular cell

Kanghyun Lee, Aye C. Thwin, Cory M. Nadel, Eric Tse, Stephanie N. Gates, Jason E. Gestwicki, Daniel R. Southworth

Practical considerations for using K3 cameras in CDS mode for high-resolution and high-throughput single particle cryo-EM.

Journal of structural biology

Sun M, Azumaya C, Tse E, Frost A, Southworth D, Verba KA, Cheng Y, Agard DA


Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.


QCRG: Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D

Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis.

Nature structural & molecular biology

Lopez KE, Rizo AN, Tse E, Lin J, Scull NW, Thwin AC, Lucius AL, Shorter J, Southworth DR




Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation.

The Journal of Biological Chemistry

Chen JJ, Nathaniel DL, Raghavan P, Nelson M, Tian R, Tse E, Hong JY, See SK, Mok SA, Hein MY, Southworth DR, Grinberg LT, Gestwicki JE, Leonetti MD, Kampmann M.

Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity.

Life Science Alliance

Lempart J, Tse E, Lauer JA, Ivanova MI, Sutter A, Yoo N, Huettemann P, Southworth D, Jakob U.

Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.

Cell reports

Tariq A, Lin J, Jackrel ME, Hesketh CD, Carman PJ, Mack KL, Weitzman R, Gambogi C, Hernandez Murillo OA, Sweeny EA, Gurpinar E, Yokom AL, Gates SN, Yee K, Sudesh S, Stillman J, Rizo AN, Southworth DR, Shorter J.

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.

Nature Communications

Rizo AN, Lin J, Gates SN, Tse E, Bart SM, Castellano LM, DiMaio F, Shorter J, Southworth DR.

Allosteric Regulation of Oligomerization by a B12 Trafficking G-Protein Is Corrupted in Methylmalonic Aciduria.

Cell Chemical Biology

Ruetz M, Campanello GC, McDevitt L, Yokom AL, Yadav PK, Watkins D, Rosenblatt DS, Ohi MD, Southworth DR, Banerjee R.

Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase.

Cold Spring Harbor Perspectives in Biology

Shorter J, Southworth DR.

Chaperone activation and client binding of a 2-cysteine peroxiredoxin.

Nature communications

Teixeira F, Tse E, Castro H, Makepeace KAT, Meinen BA, Borchers CH, Poole LB, Bardwell JC, Tomás AM, Southworth DR, Jakob U.


Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau.

Nature communications

Freilich R, Betegon M, Tse E, Mok SA, Julien O, Agard DA, Southworth DR, Takeuchi K, Gestwicki JE

Polyphosphate Stabilizes Protein Unfolding Intermediates as Soluble Amyloid-like Oligomers.

Journal of molecular biology

Yoo N, Dogra S, Meinen BA, Tse E, Haefliger J, Southworth DR, Gray MJ, Dahl JU, Jakob U

Chaperone Activity and Dimerization Properties of Hsp90a and Hsp90ß in Glucocorticoid Receptor Activation by the Multiprotein Hsp90/Hsp70-Dependent Chaperone Machinery.

Molecular pharmacology

Morishima Y, Mehta RK, Yoshimura M, Lau M, Southworth DR, Lawrence TS, Pratt WB, Nyati MK, Osawa Y

The full-length cytochrome P450 enzyme CYP102A1 dimerizes at its reductase domains and has flexible heme domains for efficient catalysis.

The Journal of biological chemistry

Zhang H, Yokom AL, Cheng S, Su M, Hollenberg PF, Southworth DR, Osawa Y

X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition.

The Journal of biological chemistry

Cesa LC, Shao H, Srinivasan SR, Tse E, Jain C, Zuiderweg ERP, Southworth DR, Mapp AK, Gestwicki JE


Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex.

The Journal of biological chemistry

Campanello GC, Lofgren M, Yokom AL, Southworth DR, Banerjee R

Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.

Science (New York, N.Y.)

Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR

BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins.

Journal of molecular biology

Rauch JN, Tse E, Freilich R, Mok SA, Makley LN, Southworth DR, Gestwicki JE


Polyphosphate: A Conserved Modifier of Amyloidogenic Processes.

Molecular cell

Cremers CM, Knoefler D, Gates S, Martin N, Dahl JU, Lempart J, Xie L, Chapman MR, Galvan V, Southworth DR, Jakob U

Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation.

Nature structural & molecular biology

Yokom AL, Gates SN, Jackrel ME, Mack KL, Su M, Shorter J, Southworth DR

Architecture and Nucleotide-Dependent Conformational Changes of the Rvb1-Rvb2 AAA+ Complex Revealed by Cryoelectron Microscopy.

Structure (London, England : 1993)

Ewens CA, Su M, Zhao L, Nano N, Houry WA, Southworth DR


Single-particle cryo-electron microscopy of macromolecular complexes.

Microscopy (Oxford, England)

Skiniotis G, Southworth DR

Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation.


Assimon VA, Southworth DR, Gestwicki JE

A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis.


Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Southworth DR, Klevit RE

Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1.

Biochimica et biophysica acta

Byers CE, Barylko B, Ross JA, Southworth DR, James NG, Taylor CA, Wang L, Collins KA, Estrada A, Waung M, Tassin TC, Huber KM, Jameson DM, Albanesi JP

Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum.

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

Teixeira F, Castro H, Cruz T, Tse E, Koldewey P, Southworth DR, Tomás AM, Jakob U


The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions.

Molecular cell

Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, Southworth DR, Schwappach B, Jakob U

Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles.


Kirschke E, Goswami D, Southworth D, Griffin PR, Agard DA

Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain.

The Journal of biological chemistry

Yokom AL, Morishima Y, Lau M, Su M, Glukhova A, Osawa Y, Southworth DR

KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated ß-TrCP1 degradation.

Neoplasia (New York, N.Y.)

Shukla S, Allam US, Ahsan A, Chen G, Krishnamurthy PM, Marsh K, Rumschlag M, Shankar S, Whitehead C, Schipper M, Basrur V, Southworth DR, Chinnaiyan AM, Rehemtulla A, Beer DG, Lawrence TS, Nyati MK, Ray D

The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain.

The Journal of biological chemistry

Connarn JN, Assimon VA, Reed RA, Tse E, Southworth DR, Zuiderweg ER, Gestwicki JE, Sun D


The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex.


Smith MC, Scaglione KM, Assimon VA, Patury S, Thompson AD, Dickey CA, Southworth DR, Paulson HL, Gestwicki JE, Zuiderweg ER


The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes the closed conformation required for ATP hydrolysis.

Protein science : a publication of the Protein Society

Cunningham CN, Southworth DR, Krukenberg KA, Agard DA


Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex.

Molecular cell

Southworth DR, Agard DA


Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide.

Protein science : a publication of the Protein Society

Krukenberg KA, Böttcher UM, Southworth DR, Agard DA

pH-dependent conformational changes in bacterial Hsp90 reveal a Grp94-like conformation at pH 6 that is highly active in suppression of citrate synthase aggregation.

Journal of molecular biology

Krukenberg KA, Southworth DR, Street TO, Agard DA


Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle.

Molecular cell

Southworth DR, Agard DA


Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome.

Journal of molecular biology

Sharma D, Cukras AR, Rogers EJ, Southworth DR, Green R


Structural Analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements.


Shiau AK, Harris SF, Southworth DR, Agard DA


EF-G-independent reactivity of a pre-translocation-state ribosome complex with the aminoacyl tRNA substrate puromycin supports an intermediate (hybrid) state of tRNA binding.

RNA (New York, N.Y.)

Sharma D, Southworth DR, Green R


Demonstration of the role of the DnaK chaperone system in assembly of 30S ribosomal subunits using a purified in vitro system.

RNA (New York, N.Y.)

Maki JA, Southworth DR, Culver GM

Ribosomal translocation: sparsomycin pushes the button.

Current biology : CB

Southworth DR, Green R

Ribosomal proteins S12 and S13 function as control elements for translocation of the mRNA:tRNA complex.

Molecular cell

Cukras AR, Southworth DR, Brunelle JL, Culver GM, Green R


EFG-independent translocation of the mRNA:tRNA complex is promoted by modification of the ribosome with thiol-specific reagents.

Journal of molecular biology

Southworth DR, Brunelle JL, Green R