Mail: BL 3035
The Biological Labs
16 Divinity Ave
Cambridge, MA 02138
Burton Lab Website
Members of the Burton Lab
List of Publications from PubMed
Term: Fall Term 2014-2015.
Instructors: Briana Burton, Vladimir Denic, Alexander Schier
Course Level: Primarily for Undergraduates
Description: This course provides an introduction to the principles of molecular and cellular biology and their connections to biomedicine. We explore how medical syndromes provide insights into biological processes and how biological mechanisms underlie human disease and physiology. Topics range from DNA repair, protein folding and vesicle transport to metabolism, cell migration and cancer. Lectures focus on the experimental evidence for key concepts, and the weekly sections combine a discovery-based laboratory research project with discussions that emphasize problem solving and primary literature.
Prerequisite(s): LPS A or LS 1a, LS 1b recommended.
Meetings: M., W., F., at 10
Term: Fall Term And Spring Term 2014-2015.
Instructor: Briana Burton
Course Level: Exclusively for Graduates
How do cells move one of the largest and most hydrophilic biological molecules across hydrophobic membrane barriers? This is the broad question our laboratory seeks to understand. In bacteria alone, this process is involved in the transfer of antibiotic resistance, spore formation, and proper chromosome segregation during growth. Yet, very little is known about the molecular mechanism of DNA translocation across membranes in any system, as tools to study the mechanism of DNA transporters in their biological context at the membrane have been lacking. We combine in vitro and in vivo biochemistry, microscopy, microbiology and molecular biology to study these DNA transport complexes.
DNA transport during sporulation
Proper chromosome segregation is essential for successful cell division in all organisms. Interestingly, bacterial cells often form a division septum prior to completion of DNA segregation. Sporulating Bacillus subtilis cells provide an extreme example of this phenomenon in that they must transport more than 3 Megabases of a chromosome across a division septum and into the small cellular compartment that will become the spore. SpoIIIE, a member of a large family of bacterial and archeal membrane-bound ATPases (FtsK/SpoIIIE), is required for active transport of the chromosomal DNA at the division septum during sporulation. Using quantitative fluorescence microscopy, and in vivo DNA transport assays to study the oligomeric state and transport properties of the SpoIIIE complex led to the very surprising and novel result that the DNA is transported across two membranes during sporulation. These data predict a new model for DNA transport in which the transmembrane segments of the transporter form linked DNA-conducting channels across the two lipid bilayers of the septum. This system provides a unique opportunity to tackle this interesting phenomenon using complimentary in vivo and in vitro approaches and to address issues which have significant implications for our understanding of how cells efficiently move of large nucleic acids across membranes.
Besprozvannaya M and Burton BM. (2014). Do the same traffic rules apply? Directional chromosome segregation by SpoIIIE and FtsK. Mol Micro, 93(4):599-608. PMID: 25040776
Ramsdell TL, Huppert LA, Fortune SM, and Burton BM. (2014). Linked Domain Architectures Allow for Specialization of Function in the FtsK/SpoIIIE ATPases of ESX Secretion Systems. J Mol Biol, pii: S0022-2836(14)00306-4. doi: 10.1016/j.jmb.2014.06.013. PMID: 24979678
Besprozvannaya M, Pivorunas VL, and Burton BM. (2014). Mechanistic Study of Classical Translocation-Dead SpoIIIE36 Reveals the Functional Importance of the Hinge within the SpoIIIE Motor. J Bacteriol, 196:2481-2490. PMCID: PMC4054170
Sysoeva TA, Zepeda-Rivera MA, Huppert LA, and Burton BM. (2014). Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis. Proc Natl Acad Sci, 111:7653-7658. PMCID: PMC4040557
Huppert LA, Ramsdell TL, Chase MR, Sarracino DA, Fortune SM, and Burton BM. (2014). The ESX System in Bacillus subtilis Mediates Protein Secretion. PLoS One, 9:e96267. PMCID: PMC4010439
Besprozvannaya, M., Pivorunas V. L., Feldman, Z., and Burton BM. (2013). SpoIIIE protein achieves directional DNA translocation through allosteric regulation of ATPase activity by an accessory domain. J. Biochem, 288 (40): 28963-28974. PMID: 23974211, PMCID: PMC3789994
Doan T, Coleman J, Marquis KA, Meeske AJ, Burton BM, Karatekin E, Rudner DZ. (2013) FisB mediates membrane fission during sporulation in Bacillus subtilis. Genes and Development, 27: 322-34. PMID: 23388828, PMCID: PMC3576517
Marquis KA, Burton BM, Nollmann M, Ptacin JL, Bustamante C, Ben-Yehuda S, Rudner DZ. (2008). SpoIIIE strips proteins off the DNA during chromosome translocation. Genes and Development, 22: 1786-1795.
Burton BM, Marquis KA, Sullivan NL, Rapoport TA, and Rudner DZ. (2007) The ATPase SpoIIIE transports DNA across fused septal membranes during sporulation in Bacillus subtilis. Cell, 131: 1301-1312.
Burton BM and Baker TA. (2005). Remodeling protein complexes: insights from the AAA+ unfoldase ClpX and Mu transposase. Protein Sci. 14:1945-1954. Review.
Sauer RT, Bolon DN, Burton BM, et al. (2004). Sculpting the proteome with AAA(+) proteases and disassembly machines. Cell, 119:9-18. Review.
Burton BM and Baker TA. (2003). Mu Transpososome Architecture Directs Unfolding by ClpX and Proteolysis by ClpXP to Remodel but Not Destroy the Complex. Chem Biol, 10; 463-472.
Burton BM, Williams TL, and Baker TA. (2001). ClpX-Mediated Remodeling of Mu Transpososomes: Selective Unfolding of Subunits Destabilizes the Entire Complex. Molecular Cell, 8; 449-454.