Faculty Appointments
Associate Professor of Pharmacology
Associate Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Molecular & Cellular Biology, University of California, Berkeley, CaliforniaB.S., Biochemistry, University of California, Davis, California
Office Address
A-4116 MCN
TN 6600
TN 6600
Research Description
The Spiller lab is a structural biology lab using protein crystallography as our main structural tool. Current questions being addressed include protein phosphatases, bacterial pathogenesis, and the host immune response. Potential rotation projects will be designed to meet the interests of the students, but will generally fall into one of the aforementioned topics. Of particular current interest is extending our work on bacterial pathogenesis.
Research Keywords
Structural Biology of virulence factors, host-pathogen relationship, and cytoskeletal regulation.
Publications
LeNoue-Newton ML, Wadzinski BE, Spiller BW. The three Type 2A protein phosphatases, PP2Ac, PP4c and PP6c, are differentially regulated by Alpha4. Biochem. Biophys. Res. Commun [print-electronic]. 2016 Jun 6/17/2016; 475(1): 64-9. PMID: 27169767, PII: S0006-291X(16)30728-8, DOI: 10.1016/j.bbrc.2016.05.036, ISSN: 1090-2104.
Winarski KL, Thornburg NJ, Yu Y, Sapparapu G, Crowe JE, Spiller BW. Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Jul 7/28/2015; 112(30): 9346-51. PMID: 26170302, PMCID: PMC4522792, PII: 1502762112, DOI: 10.1073/pnas.1502762112, ISSN: 1091-6490.
Archuleta TL, Spiller BW. A gatekeeper chaperone complex directs translocator secretion during type three secretion. PLoS Pathog. 2014 Nov; 10(11): e1004498. PMID: 25375170, PMCID: PMC4222845, PII: PPATHOGENS-D-14-01796, DOI: 10.1371/journal.ppat.1004498, ISSN: 1553-7374.
Markadieu N, Rios K, Spiller BW, McDonald WH, Welling PA, Delpire E. Short forms of Ste20-related proline/alanine-rich kinase (SPAK) in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage. J. Biol. Chem [print-electronic]. 2014 Oct 10/17/2014; 289(42): 29273-84. PMID: 25164821, PMCID: PMC4200278, PII: M114.604009, DOI: 10.1074/jbc.M114.604009, ISSN: 1083-351X.
Aiyegbo MS, Eli IM, Spiller BW, Williams DR, Kim R, Lee DE, Liu T, Li S, Stewart PL, Crowe JE. Differential accessibility of a rotavirus VP6 epitope in trimers comprising type I, II, or III channels as revealed by binding of a human rotavirus VP6-specific antibody. J. Virol [print-electronic]. 2014 Jan; 88(1): 469-76. PMID: 24155406, PMCID: PMC3911710, PII: JVI.01665-13, DOI: 10.1128/JVI.01665-13, ISSN: 1098-5514.
Aiyegbo MS, Sapparapu G, Spiller BW, Eli IM, Williams DR, Kim R, Lee DE, Liu T, Li S, Woods VL, Nannemann DP, Meiler J, Stewart PL, Crowe JE. Human rotavirus VP6-specific antibodies mediate intracellular neutralization by binding to a quaternary structure in the transcriptional pore. PLoS ONE [electronic-print]. 2013; 8(5): e61101. PMID: 23671563, PMCID: PMC3650007, PII: PONE-D-13-06430, DOI: 10.1371/journal.pone.0061101, ISSN: 1932-6203.
Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit a4, altering PP2A stability and microtubule-associated protein phosphorylation. J. Biol. Chem [print-electronic]. 2012 Jul 7/13/2012; 287(29): 24207-15. PMID: 22613722, PMCID: PMC3397847, PII: M112.368613, DOI: 10.1074/jbc.M112.368613, ISSN: 1083-351X.
McHaourab HS, Lin YL, Spiller BW. Crystal structure of an activated variant of small heat shock protein Hsp16.5. Biochemistry [print-electronic]. 2012 Jun 6/26/2012; 51(25): 5105-12. PMID: 22670769, PMCID: PMC3384710, DOI: 10.1021/bi300525x, ISSN: 1520-4995.
Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, Spiller B, Lacy DB. Structural determinants of Clostridium difficile toxin A glucosyltransferase activity. J. Biol. Chem [print-electronic]. 2012 Mar 3/9/2012; 287(11): 8013-20. PMID: 22267739, PMCID: PMC3318759, PII: M111.298414, DOI: 10.1074/jbc.M111.298414, ISSN: 1083-351X.
Archuleta TL, Du Y, English CA, Lory S, Lesser C, Ohi MD, Ohi R, Spiller BW. The Chlamydia effector chlamydial outer protein N (CopN) sequesters tubulin and prevents microtubule assembly. J. Biol. Chem [print-electronic]. 2011 Sep 9/30/2011; 286(39): 33992-8. PMID: 21841198, PMCID: PMC3190796, PII: M111.258426, DOI: 10.1074/jbc.M111.258426, ISSN: 1083-351X.
Coffa S, Breitman M, Spiller BW, Gurevich VV. A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1 binding. Biochemistry [print-electronic]. 2011 Aug 8/16/2011; 50(32): 6951-8. PMID: 21732673, PMCID: PMC3153575, DOI: 10.1021/bi200745k, ISSN: 1520-4995.
LeNoue-Newton M, Watkins GR, Zou P, Germane KL, McCorvey LR, Wadzinski BE, Spiller BW. The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. J. Biol. Chem [print-electronic]. 2011 May 5/20/2011; 286(20): 17665-71. PMID: 21454489, PMCID: PMC3093842, PII: M111.222414, DOI: 10.1074/jbc.M111.222414, ISSN: 1083-351X.
Zhan X, Gimenez LE, Gurevich VV, Spiller BW. Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes. J. Mol. Biol [print-electronic]. 2011 Feb 2/25/2011; 406(3): 467-78. PMID: 21215759, PMCID: PMC3034793, PII: S0022-2836(10)01366-5, DOI: 10.1016/j.jmb.2010.12.034, ISSN: 1089-8638.
Germane KL, Spiller BW. Structural and functional studies indicate that the EPEC effector, EspG, directly binds p21-activated kinase. Biochemistry [print-electronic]. 2011 Feb 2/15/2011; 50(6): 917-9. PMID: 21235237, PMCID: PMC3040069, DOI: 10.1021/bi1020138, ISSN: 1520-4995.
Schmitt J, Karalewitz A, Benefield DA, Mushrush DJ, Pruitt RN, Spiller BW, Barbieri JT, Lacy DB. Structural analysis of botulinum neurotoxin type G receptor binding. Biochemistry. 2010 Jun 6/29/2010; 49(25): 5200-5. PMID: 20507178, PMCID: PMC2894633, DOI: 10.1021/bi100412v, ISSN: 1520-4995.
McConnell JL, Watkins GR, Soss SE, Franz HS, McCorvey LR, Spiller BW, Chazin WJ, Wadzinski BE. Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry. 2010 Mar 3/2/2010; 49(8): 1713-8. PMID: 20092282, PMCID: PMC2832797, DOI: 10.1021/bi901837h, ISSN: 1520-4995.
Pruitt RN, Chagot B, Cover M, Chazin WJ, Spiller B, Lacy DB. Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. J. Biol. Chem [print-electronic]. 2009 Aug 8/14/2009; 284(33): 21934-40. PMID: 19553670, PMCID: PMC2755918, PII: M109.018929, DOI: 10.1074/jbc.M109.018929, ISSN: 0021-9258.
Germane KL, Ohi R, Goldberg MB, Spiller BW. Structural and functional studies indicate that Shigella VirA is not a protease and does not directly destabilize microtubules. Biochemistry [print-electronic]. 2008 Sep 9/30/2008; 47(39): 10241-3. PMID: 18763811, PMCID: PMC4096815, DOI: 10.1021/bi801533k, ISSN: 1520-4995.
Fujinami S, Sato T, Trimmer JS, Spiller BW, Clapham DE, Krulwich TA, Kawagishi I, Ito M. The voltage-gated Na+ channel NaVBP co-localizes with methyl-accepting chemotaxis protein at cell poles of alkaliphilic Bacillus pseudofirmus OF4. Microbiology (Reading, Engl.). 2007 Dec; 153(Pt 12): 4027-38. PMID: 18048917, PMCID: PMC2556953, PII: 153/12/4027, DOI: 10.1099/mic.0.2007/012070-0, ISSN: 1350-0872.
Gangwer KA, Mushrush DJ, Stauff DL, Spiller B, McClain MS, Cover TL, Lacy DB. Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Oct 10/9/2007; 104(41): 16293-8. PMID: 17911250, PMCID: PMC2042200, PII: 0707447104, DOI: 10.1073/pnas.0707447104, ISSN: 0027-8424.
Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q, Clapham DE. A superfamily of voltage-gated sodium channels in bacteria. J. Biol. Chem [print-electronic]. 2004 Mar 3/5/2004; 279(10): 9532-8. PMID: 14665618, PII: M313100200, DOI: 10.1074/jbc.M313100200, ISSN: 0021-9258.
Spiller B, Gershenson A, Arnold FH, Stevens RC. A structural view of evolutionary divergence. Proc. Natl. Acad. Sci. U.S.A. 1999 Oct 10/26/1999; 96(22): 12305-10. PMID: 10535917, PMCID: PMC22912, ISSN: 0027-8424.
Romesberg FE, Santarsiero BD, Spiller B, Yin J, Barnes D, Schultz PG, Stevens RC. Structural and kinetic evidence for strain in biological catalysis. Biochemistry. 1998 Oct 10/13/1998; 37(41): 14404-9. PMID: 9772166, PII: bi981578c, DOI: 10.1021/bi981578c, ISSN: 0006-2960.
Romesberg FE, Spiller B, Schultz PG, Stevens RC. Immunological origins of binding and catalysis in a Diels-Alderase antibody. Science. 1998 Mar 3/20/1998; 279(5358): 1929-33. PMID: 9506942, ISSN: 0036-8075.
R.C. Stevens, L.C. Hsieh-Wilson, B.D. Santarsiero, G.J. Wedemayer, B. Spiller, L.H. Wang, D. Barnes, H.D. Ulrich, P.A. Patten, F.E. Romesberg, and P.G. Schultz. Structural Studies of Catalytic Antibodies. Israel Journal of Chemistry. 1996; 36: 121-32.
Winarski KL, Thornburg NJ, Yu Y, Sapparapu G, Crowe JE, Spiller BW. Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Jul 7/28/2015; 112(30): 9346-51. PMID: 26170302, PMCID: PMC4522792, PII: 1502762112, DOI: 10.1073/pnas.1502762112, ISSN: 1091-6490.
Archuleta TL, Spiller BW. A gatekeeper chaperone complex directs translocator secretion during type three secretion. PLoS Pathog. 2014 Nov; 10(11): e1004498. PMID: 25375170, PMCID: PMC4222845, PII: PPATHOGENS-D-14-01796, DOI: 10.1371/journal.ppat.1004498, ISSN: 1553-7374.
Markadieu N, Rios K, Spiller BW, McDonald WH, Welling PA, Delpire E. Short forms of Ste20-related proline/alanine-rich kinase (SPAK) in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage. J. Biol. Chem [print-electronic]. 2014 Oct 10/17/2014; 289(42): 29273-84. PMID: 25164821, PMCID: PMC4200278, PII: M114.604009, DOI: 10.1074/jbc.M114.604009, ISSN: 1083-351X.
Aiyegbo MS, Eli IM, Spiller BW, Williams DR, Kim R, Lee DE, Liu T, Li S, Stewart PL, Crowe JE. Differential accessibility of a rotavirus VP6 epitope in trimers comprising type I, II, or III channels as revealed by binding of a human rotavirus VP6-specific antibody. J. Virol [print-electronic]. 2014 Jan; 88(1): 469-76. PMID: 24155406, PMCID: PMC3911710, PII: JVI.01665-13, DOI: 10.1128/JVI.01665-13, ISSN: 1098-5514.
Aiyegbo MS, Sapparapu G, Spiller BW, Eli IM, Williams DR, Kim R, Lee DE, Liu T, Li S, Woods VL, Nannemann DP, Meiler J, Stewart PL, Crowe JE. Human rotavirus VP6-specific antibodies mediate intracellular neutralization by binding to a quaternary structure in the transcriptional pore. PLoS ONE [electronic-print]. 2013; 8(5): e61101. PMID: 23671563, PMCID: PMC3650007, PII: PONE-D-13-06430, DOI: 10.1371/journal.pone.0061101, ISSN: 1932-6203.
Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit a4, altering PP2A stability and microtubule-associated protein phosphorylation. J. Biol. Chem [print-electronic]. 2012 Jul 7/13/2012; 287(29): 24207-15. PMID: 22613722, PMCID: PMC3397847, PII: M112.368613, DOI: 10.1074/jbc.M112.368613, ISSN: 1083-351X.
McHaourab HS, Lin YL, Spiller BW. Crystal structure of an activated variant of small heat shock protein Hsp16.5. Biochemistry [print-electronic]. 2012 Jun 6/26/2012; 51(25): 5105-12. PMID: 22670769, PMCID: PMC3384710, DOI: 10.1021/bi300525x, ISSN: 1520-4995.
Pruitt RN, Chumbler NM, Rutherford SA, Farrow MA, Friedman DB, Spiller B, Lacy DB. Structural determinants of Clostridium difficile toxin A glucosyltransferase activity. J. Biol. Chem [print-electronic]. 2012 Mar 3/9/2012; 287(11): 8013-20. PMID: 22267739, PMCID: PMC3318759, PII: M111.298414, DOI: 10.1074/jbc.M111.298414, ISSN: 1083-351X.
Archuleta TL, Du Y, English CA, Lory S, Lesser C, Ohi MD, Ohi R, Spiller BW. The Chlamydia effector chlamydial outer protein N (CopN) sequesters tubulin and prevents microtubule assembly. J. Biol. Chem [print-electronic]. 2011 Sep 9/30/2011; 286(39): 33992-8. PMID: 21841198, PMCID: PMC3190796, PII: M111.258426, DOI: 10.1074/jbc.M111.258426, ISSN: 1083-351X.
Coffa S, Breitman M, Spiller BW, Gurevich VV. A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1 binding. Biochemistry [print-electronic]. 2011 Aug 8/16/2011; 50(32): 6951-8. PMID: 21732673, PMCID: PMC3153575, DOI: 10.1021/bi200745k, ISSN: 1520-4995.
LeNoue-Newton M, Watkins GR, Zou P, Germane KL, McCorvey LR, Wadzinski BE, Spiller BW. The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. J. Biol. Chem [print-electronic]. 2011 May 5/20/2011; 286(20): 17665-71. PMID: 21454489, PMCID: PMC3093842, PII: M111.222414, DOI: 10.1074/jbc.M111.222414, ISSN: 1083-351X.
Zhan X, Gimenez LE, Gurevich VV, Spiller BW. Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes. J. Mol. Biol [print-electronic]. 2011 Feb 2/25/2011; 406(3): 467-78. PMID: 21215759, PMCID: PMC3034793, PII: S0022-2836(10)01366-5, DOI: 10.1016/j.jmb.2010.12.034, ISSN: 1089-8638.
Germane KL, Spiller BW. Structural and functional studies indicate that the EPEC effector, EspG, directly binds p21-activated kinase. Biochemistry [print-electronic]. 2011 Feb 2/15/2011; 50(6): 917-9. PMID: 21235237, PMCID: PMC3040069, DOI: 10.1021/bi1020138, ISSN: 1520-4995.
Schmitt J, Karalewitz A, Benefield DA, Mushrush DJ, Pruitt RN, Spiller BW, Barbieri JT, Lacy DB. Structural analysis of botulinum neurotoxin type G receptor binding. Biochemistry. 2010 Jun 6/29/2010; 49(25): 5200-5. PMID: 20507178, PMCID: PMC2894633, DOI: 10.1021/bi100412v, ISSN: 1520-4995.
McConnell JL, Watkins GR, Soss SE, Franz HS, McCorvey LR, Spiller BW, Chazin WJ, Wadzinski BE. Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry. 2010 Mar 3/2/2010; 49(8): 1713-8. PMID: 20092282, PMCID: PMC2832797, DOI: 10.1021/bi901837h, ISSN: 1520-4995.
Pruitt RN, Chagot B, Cover M, Chazin WJ, Spiller B, Lacy DB. Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. J. Biol. Chem [print-electronic]. 2009 Aug 8/14/2009; 284(33): 21934-40. PMID: 19553670, PMCID: PMC2755918, PII: M109.018929, DOI: 10.1074/jbc.M109.018929, ISSN: 0021-9258.
Germane KL, Ohi R, Goldberg MB, Spiller BW. Structural and functional studies indicate that Shigella VirA is not a protease and does not directly destabilize microtubules. Biochemistry [print-electronic]. 2008 Sep 9/30/2008; 47(39): 10241-3. PMID: 18763811, PMCID: PMC4096815, DOI: 10.1021/bi801533k, ISSN: 1520-4995.
Fujinami S, Sato T, Trimmer JS, Spiller BW, Clapham DE, Krulwich TA, Kawagishi I, Ito M. The voltage-gated Na+ channel NaVBP co-localizes with methyl-accepting chemotaxis protein at cell poles of alkaliphilic Bacillus pseudofirmus OF4. Microbiology (Reading, Engl.). 2007 Dec; 153(Pt 12): 4027-38. PMID: 18048917, PMCID: PMC2556953, PII: 153/12/4027, DOI: 10.1099/mic.0.2007/012070-0, ISSN: 1350-0872.
Gangwer KA, Mushrush DJ, Stauff DL, Spiller B, McClain MS, Cover TL, Lacy DB. Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Oct 10/9/2007; 104(41): 16293-8. PMID: 17911250, PMCID: PMC2042200, PII: 0707447104, DOI: 10.1073/pnas.0707447104, ISSN: 0027-8424.
Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q, Clapham DE. A superfamily of voltage-gated sodium channels in bacteria. J. Biol. Chem [print-electronic]. 2004 Mar 3/5/2004; 279(10): 9532-8. PMID: 14665618, PII: M313100200, DOI: 10.1074/jbc.M313100200, ISSN: 0021-9258.
Spiller B, Gershenson A, Arnold FH, Stevens RC. A structural view of evolutionary divergence. Proc. Natl. Acad. Sci. U.S.A. 1999 Oct 10/26/1999; 96(22): 12305-10. PMID: 10535917, PMCID: PMC22912, ISSN: 0027-8424.
Romesberg FE, Santarsiero BD, Spiller B, Yin J, Barnes D, Schultz PG, Stevens RC. Structural and kinetic evidence for strain in biological catalysis. Biochemistry. 1998 Oct 10/13/1998; 37(41): 14404-9. PMID: 9772166, PII: bi981578c, DOI: 10.1021/bi981578c, ISSN: 0006-2960.
Romesberg FE, Spiller B, Schultz PG, Stevens RC. Immunological origins of binding and catalysis in a Diels-Alderase antibody. Science. 1998 Mar 3/20/1998; 279(5358): 1929-33. PMID: 9506942, ISSN: 0036-8075.
R.C. Stevens, L.C. Hsieh-Wilson, B.D. Santarsiero, G.J. Wedemayer, B. Spiller, L.H. Wang, D. Barnes, H.D. Ulrich, P.A. Patten, F.E. Romesberg, and P.G. Schultz. Structural Studies of Catalytic Antibodies. Israel Journal of Chemistry. 1996; 36: 121-32.
Available Postdoctoral Position Details
Posted: 6/21/2016
We seek a highly motivated postdoctoral fellow interested in Structural Biology and Bacterial Pathogenesis. The focus will be on one of multiple projects involving pathogenesis in Gram-negative bacterial. We employ a diverse set of approaches to study pathogenesis, but a focus involves structural studies of relevant pathogen or host proteins. High impact projects with strong preliminary data are currently available. Interested parties should send a cover letter and CV to benjamin.spiller@vanderbilt.edu