Brian Downes, Ph.D.
Cell Structure and Function, Molecular Biology, Advanced Molecular Biology
Ph.D. Purdue University
The lab is studying new layers of specificity for the ubiquitin system, which is a
major selector for regulatory protein modification and degradation. Downes and his
colleagues are currently focused on a small ubiquitin-fold protein, which they named
MUB, short for Membrane-anchored Ubiquitin-fold. MUBs from diverse organisms are modified
with a hydrophobic prenyl tail that allows MUBs to move specific components of the
ubiquitylation system to the plasma membrane, which is adjacent to a multitude of
critical regulatory proteins. These functions appear to be highly conserved, demonstrated,
so far, for both plant (Arabidopsis thaliana) and human MUB proteins. As modulators of the ubiquitin system, understanding MUB
function may reveal new mechanisms used in eukaryotic protein modification and inform
efforts to improve our agricultural and medical practices.
Many of Downes's studies use Arabidopsis thaliana, a model eukaryote with numerous advantages for the genetic, genomic, molecular and biochemical approaches that we take. Core discoveries are typically recapitulated with human proteins to determine the extent of functional conservation. Downes and colleagues are actively working to (i) discover additional MUB-interacting proteins, (ii) to understand if MUBs change the activity of interacting proteins, and (iii) to determine the structural characteristics of MUB/protein complexes as they target the plasma membrane peripheral space.
Labs and Facilities
A number of exciting projects are currently underway. Researchers in the Downes Lab develop technical skills in bioinformatics, biochemistry, molecular biology and genetics. As expertise develops independent hypothesis driven projects are pursued. Inquiries concerning undergraduate, graduate and post-graduate work are welcome.
Publications and Media Placements
Lu X, Malley KR, Brenner CC, Koroleva O, Korolev S, Downes BP (2016) A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes. Nat Commun 7, 12580.
Dowil RT, Lu X, Saracco SA, Vierstra RD, Downes BP (2011) Arabidopsis Membrane-Anchored Ubiquitin-Fold (MUB) Proteins Localize A Specific Subset of Ubiquitin-Conjugating (E2) Enzymes to the Plasma Membrane. J Biol Chem. 286: 14913-14921.
Grojean J, Downes BP (2010) Riboswitches as Receptors: Candidate Cytokinin-Binding Riboswitches in Arabidopsis thaliana. Biology Direct. 5: 60 pp.1-12.
Downes BP, Saracco SA, Lee SS, Crowell DN, Vierstra RD (2006) MUBs: a unique family of ubiquitin-fold proteins that are membrane-anchored by prenylation. J Biol Chem. 281: 27145-27157.
Downes BP and Vierstra RD (2005) Post-translational regulation in plants employing a diverse set of polpeptide tags. Biochem Soc Trans. 33: 393-399.
Downes BP, Stupar RM, Gingerich DJ, Vierstra RD (2003) The HECT ubiquitin-protein ligase (UPL) family in Arabidopsis: UPL3 has a specific role in trichome development. Plant J. 35: 729-742.
Crowell DN, Packard CE, Pierson CA, Giner JL, Downes BP, Chary SN (2003) Identification of an allele of CLA1 associated with variegation in Arabidopsis thaliana. Physiol Plant. 118: 29-37.
Gagne JM, Downes BP, Shiu SH, Durski AM, Vierstra RD (2002) The F-box subunit of the SCF E3 complex is encoded by a diverse superfamily of genes in Arabidopsis. Proc Natl Acad Sci U S A. 99: 11519-11524.
Downes BP, Steinbaker CR, Crowell DN (2001) Expression and processing of a hormonally regulated beta-expansin from soybean. Plant Physiol. 126: 244-252.
Downes BP and Crowell DN (1998) Cytokinin regulates the expression of a beta-expansin gene by a posttranscriptional mechanism. Plant Mol Biol. 37: 437-444.