Breann Leigh Brown, Ph.D.

Assistant Professor

breann.brown@vanderbilt.edu

Visit Lab Site


Faculty Appointments
Assistant Professor of Biochemistry
Education
Ph.D., Molecular Pharmacology and Physiology, Brown University, Providence, Rhode IslandB.S., Chemistry, Duke University, Durham, North Carolina
Office Address
639C Light Hall
2215 Garland Avenue
Nashville, TN 37204
Research Description
Macromolecular protein complex assembly is critical for maintaining human health. These precise interactions are necessary for modulating various cellular processes such as activity of signaling pathways, providing feedback regulation, and mediating transport and transfer of molecules among partners. Unfortunately, there are numerous painful, debilitating, and life-threatening diseases that occur due to genetic mutations that prevent proper protein assembly. Our approach is to use X-ray crystallography and other complementary biochemical techniques to understand how these various mutations lead to changes in protein structure and function, thus preventing productive macromolecular assembly. We focus on areas of human health related to mitochondrial biology and metabolism. Specifically, we seek to understand assembly mechanisms responsible for regulation of heme biosynthesis, which is altered in several blood diseases, and maintenance of mitochondrial DNA copy number, which has implications in proper neuronal development.
Research Keywords
X-ray crystallography, mitochondria, protein structure-function, heme, neurodegenerative diseases, structural biology, biophysics
Publications
Brown BL, Vieux EF, Kalastavadi T, Kim S, Chen JZ, Baker TA. N domain of the Lon AAA+ protease controls assembly and substrate choice. Protein Sci [print-electronic]. 2018 Nov 11/21/2018; PMID: 30461098, DOI: 10.1002/pro.3553, ISSN: 1469-896X.

Brown BL, Kardon JR, Sauer RT, Baker TA. Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme. Structure [print-electronic]. 2018 Apr 4/3/2018; 26(4): 580-589.e4. PMID: 29551290, PMCID: PMC5894356, PII: S0969-2126(18)30052-2, DOI: 10.1016/j.str.2018.02.012, ISSN: 1878-4186.

Davis JR, Brown BL, Page R, Sello JK. Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors. Nucleic Acids Res [print-electronic]. 2013 Apr 4/1/2013; 41(6): 3888-900. PMID: 23396446, PMCID: PMC3616709, PII: gkt009, DOI: 10.1093/nar/gkt009, ISSN: 1362-4962.

Brown BL, Lord DM, Grigoriu S, Peti W, Page R. The Escherichia coli toxin MqsR destabilizes the transcriptional repression complex formed between the antitoxin MqsA and the mqsRA operon promoter. J. Biol. Chem [print-electronic]. 2013 Jan 1/11/2013; 288(2): 1286-94. PMID: 23172222, PMCID: PMC3543012, PII: M112.421008, DOI: 10.1074/jbc.M112.421008, ISSN: 1083-351X.

Wang X, Kim Y, Hong SH, Ma Q, Brown BL, Pu M, Tarone AM, Benedik MJ, Peti W, Page R, Wood TK. Antitoxin MqsA helps mediate the bacterial general stress response. Nat. Chem. Biol [print-electronic]. 2011 Jun; 7(6): 359-66. PMID: 21516113, PMCID: PMC3097263, PII: nchembio.560, DOI: 10.1038/nchembio.560, ISSN: 1552-4469.

Brown BL, Wood TK, Peti W, Page R. Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation. J. Biol. Chem [print-electronic]. 2011 Jan 1/21/2011; 286(3): 2285-96. PMID: 21068382, PMCID: PMC3023523, PII: M110.172643, DOI: 10.1074/jbc.M110.172643, ISSN: 1083-351X.

Brown BL, Page R. Preliminary crystallographic analysis of the Escherichia coli antitoxin MqsA (YgiT/b3021) in complex with mqsRA promoter DNA. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun [print-electronic]. 2010 Sep 9/1/2010; 66(Pt 9): 1060-3. PMID: 20823526, PMCID: PMC2935227, PII: S1744309110028617, DOI: 10.1107/S1744309110028617, ISSN: 1744-3091.

Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R. Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties. PLoS Pathog [print-electronic]. 2009 Dec; 5(12): e1000706. PMID: 20041169, PMCID: PMC2791442, DOI: 10.1371/journal.ppat.1000706, ISSN: 1553-7374.

Brown BL, Hadley M, Page R. Heterologous high-level E. coli expression, purification and biophysical characterization of the spine-associated RapGAP (SPAR) PDZ domain. Protein Expr. Purif [print-electronic]. 2008 Nov; 62(1): 9-14. PMID: 18678258, PII: S1046-5928(08)00179-4, DOI: 10.1016/j.pep.2008.07.003, ISSN: 1096-0279.