Daniel Southworth, PhD

TitleAssociate Professor
InstitutionUniversity of California San Francisco
DepartmentInstitute for Neurodegenerative Diseases
Address675 Nelson Rising Lane
San Francisco CA 94158
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    Collapse Biography 
    Collapse Awards and Honors
    American Heart Association2013  - 2016Top Scientist Development Award
    Alzheimer's Association2012  - 2014New Investigator Award
    University of Michigan2011Biological Sciences Scholar
    American Cancer Society2007  - 2010Postdoctoral Fellowship
    Johns Hopkins University2004Paul Ehrlich Research Award

    Collapse Research 
    Collapse Research Activities and Funding
    The molecular mechanisms of nutrient- and stress-dependent mTORC1 regulation mediated by human Sestrin2.
    NIH R01DK111465Sep 19, 2016 - Aug 31, 2021
    Role: Co-Investigator
    Defining the conformational cycle of nitric oxide synthases
    NIH/NIGMS R01GM110001Sep 1, 2015 - Aug 31, 2020
    Role: Principal Investigator
    Exploration of Molecular Chaperone Complexes During Active Protein Triage
    NIH/NIGMS R01GM109896Jun 1, 2014 - Feb 28, 2018
    Role: Co-Investigator
    Mechanisms of motor neuron toxicity in Kennedy disease
    NIH/NINDS R01NS055746Mar 5, 2007 - Apr 30, 2022
    Role: Co-Principal Investigator
    Mechanisms of Activation for Human Small Heat Shock Proteins: An Integrated Approach
    NIH R01EY017370Apr 1, 2006 - Jun 30, 2020
    Role: Co-Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Morishima Y, Mehta RK, Yoshimura M, Lau M, Southworth D, Lawrence TS, Pratt WB, Nyati MK, Osawa Y. Chaperone Activity and Dimerization Properties of Hsp90a and Hsp90ß in Glucocorticoid Receptor Activation by the Multiprotein Hsp90/Hsp70-Dependent Chaperone Machinery. Mol Pharmacol. 2018 Jun 25. PMID: 29941666.
      View in: PubMed
    2. Zhang H, Yokom AL, Cheng S, Su M, Hollenberg PF, Southworth D, Osawa Y. The full-length cytochrome P450 enzyme CYP102A1 dimerizes at its reductase domains and has flexible heme domains for efficient catalysis. J Biol Chem. 2018 Apr 04. PMID: 29618513.
      View in: PubMed
    3. Cesa LC, Shao H, Srinivasan SR, Tse E, Jain C, Zuiderweg ERP, Southworth D, Mapp AK, Gestwicki JE. X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition. J Biol Chem. 2018 Feb 16; 293(7):2370-2380. PMID: 29255093.
      View in: PubMed
    4. Campanello GC, Lofgren M, Yokom AL, Southworth D, Banerjee R. Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex. J Biol Chem. 2017 10 27; 292(43):17617-17625. PMID: 28882898.
      View in: PubMed
    5. 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 D. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science. 2017 07 21; 357(6348):273-279. PMID: 28619716.
      View in: PubMed
    6. Rauch JN, Tse E, Freilich R, Mok SA, Makley LN, Southworth D, Gestwicki JE. BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins. J Mol Biol. 2017 01 06; 429(1):128-141. PMID: 27884606.
      View in: PubMed
    7. Cremers CM, Knoefler D, Gates S, Martin N, Dahl JU, Lempart J, Xie L, Chapman MR, Galvan V, Southworth D, Jakob U. Polyphosphate: A Conserved Modifier of Amyloidogenic Processes. Mol Cell. 2016 09 01; 63(5):768-80. PMID: 27570072.
      View in: PubMed
    8. Yokom AL, Gates SN, Jackrel ME, Mack KL, Su M, Shorter J, Southworth D. Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation. Nat Struct Mol Biol. 2016 09; 23(9):830-7. PMID: 27478928.
      View in: PubMed
    9. Ewens CA, Su M, Zhao L, Nano N, Houry WA, Southworth D. Architecture and Nucleotide-Dependent Conformational Changes of the Rvb1-Rvb2 AAA+ Complex Revealed by Cryoelectron Microscopy. Structure. 2016 05 03; 24(5):657-666. PMID: 27112599.
      View in: PubMed
    10. Assimon VA, Southworth D, Gestwicki JE. Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation. Biochemistry. 2015 Dec 08; 54(48):7120-31. PMID: 26565746; PMCID: PMC4714923 [Available on 12/08/16].
    11. Skiniotis G, Southworth D. Single-particle cryo-electron microscopy of macromolecular complexes. Microscopy (Oxf). 2016 Feb; 65(1):9-22. PMID: 26611544.
      View in: PubMed
    12. Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Southworth D, Klevit RE. A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis. Elife. 2015 May 11; 4. PMID: 25962097; PMCID: PMC4456606.
    13. Byers CE, Barylko B, Ross JA, Southworth D, James NG, Taylor CA, Wang L, Collins KA, Estrada A, Waung M, Tassin TC, Huber KM, Jameson DM, Albanesi JP. Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1. Biochim Biophys Acta. 2015 Jun; 1850(6):1310-8. PMID: 25783003; PMCID: PMC4398645.
    14. Teixeira F, Castro H, Cruz T, Tse E, Koldewey P, Southworth D, Tomás AM, Jakob U. Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum. Proc Natl Acad Sci U S A. 2015 Feb 17; 112(7):E616-24. PMID: 25646478; PMCID: PMC4343147.
    15. Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, Southworth D, Schwappach B, Jakob U. The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Mol Cell. 2014 Oct 02; 56(1):116-27. PMID: 25242142; PMCID: PMC4204210.
    16. Kirschke E, Goswami D, Southworth D, Griffin PR, Agard DA. Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell. 2014 Jun 19; 157(7):1685-97. PMID: 24949977; PMCID: PMC4087167.
    17. Yokom AL, Morishima Y, Lau M, Su M, Glukhova A, Osawa Y, Southworth D. Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain. J Biol Chem. 2014 Jun 13; 289(24):16855-65. PMID: 24737326; PMCID: PMC4059128.
    18. Shukla S, Allam US, Ahsan A, Chen G, Krishnamurthy PM, Marsh K, Rumschlag M, Shankar S, Whitehead C, Schipper M, Basrur V, Southworth D, Chinnaiyan AM, Rehemtulla A, Beer DG, Lawrence TS, Nyati MK, Ray D. KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated ß-TrCP1 degradation. Neoplasia. 2014 Feb; 16(2):115-28. PMID: 24709419; PMCID: PMC3978392.
    19. Connarn JN, Assimon VA, Reed RA, Tse E, Southworth D, Zuiderweg ER, Gestwicki JE, Sun D. The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain. J Biol Chem. 2014 Jan 31; 289(5):2908-17. PMID: 24327656; PMCID: PMC3908423.
    20. Smith MC, Scaglione KM, Assimon VA, Patury S, Thompson AD, Dickey CA, Southworth D, Paulson HL, Gestwicki JE, Zuiderweg ER. The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex. Biochemistry. 2013 Aug 13; 52(32):5354-64. PMID: 23865999; PMCID: PMC3856692.
    21. Cunningham CN, Southworth D, Krukenberg KA, Agard DA. The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes the closed conformation required for ATP hydrolysis. Protein Sci. 2012 Aug; 21(8):1162-71. PMID: 22653663; PMCID: PMC3537237.
    22. Southworth D, Agard DA. Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex. Mol Cell. 2011 Jun 24; 42(6):771-81. PMID: 21700222; PMCID: PMC3144320.
    23. Krukenberg KA, Böttcher UM, Southworth D, Agard DA. Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide. Protein Sci. 2009 Sep; 18(9):1815-27. PMID: 19554567; PMCID: PMC2777357.
    24. Krukenberg KA, Southworth D, Street TO, 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. J Mol Biol. 2009 Jul 10; 390(2):278-91. PMID: 19427321; PMCID: PMC2735500.
    25. Southworth D, Agard DA. Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle. Mol Cell. 2008 Dec 05; 32(5):631-40. PMID: 19061638; PMCID: PMC2633443.
    26. Sharma D, Cukras AR, Rogers EJ, Southworth D, Green R. Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome. J Mol Biol. 2007 Dec 07; 374(4):1065-76. PMID: 17967466; PMCID: PMC2200631.
    27. Shiau AK, Harris SF, Southworth D, Agard DA. Structural Analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements. Cell. 2006 Oct 20; 127(2):329-40. PMID: 17055434.
      View in: PubMed
    28. Sharma D, Southworth D, Green R. 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. 2004 Jan; 10(1):102-13. PMID: 14681589; PMCID: PMC1370522.
    29. Maki JA, Southworth D, Culver GM. Demonstration of the role of the DnaK chaperone system in assembly of 30S ribosomal subunits using a purified in vitro system. RNA. 2003 Dec; 9(12):1418-21. PMID: 14623997; PMCID: PMC1370495.
    30. Southworth D, Green R. Ribosomal translocation: sparsomycin pushes the button. Curr Biol. 2003 Aug 19; 13(16):R652-4. PMID: 12932345.
      View in: PubMed
    31. Cukras AR, Southworth D, Brunelle JL, Culver GM, Green R. Ribosomal proteins S12 and S13 function as control elements for translocation of the mRNA:tRNA complex. Mol Cell. 2003 Aug; 12(2):321-8. PMID: 14536072.
      View in: PubMed
    32. Southworth D, Brunelle JL, Green R. EFG-independent translocation of the mRNA:tRNA complex is promoted by modification of the ribosome with thiol-specific reagents. J Mol Biol. 2002 Dec 06; 324(4):611-23. PMID: 12460565.
      View in: PubMed