Francis Tsai, D.Phil
Professor, Biochemistry, Molecular and Cellular Biology, & Molecular Biology
Baylor College of Medicine
B.Sc. (Joint Hons) Chemistry & Biochemistry, Imperial College London (1993)
D.Phil. Biochemistry, Oxford University (1997)
Wellcome Trust Postdoctoral Fellow, Yale University/HHMI (Sigler Lab; 1996-2000)
Proteins must fold correctly in order to attain biological function. Concurrently, protein misfolding and aggregation are primary contributors to many human neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and transmissible spongiform encephalopathy (TSE), better known as the human form of "Mad Cow Disease". Molecular chaperones, such as Hsp60 (GroEL), Hsp70 (DnaK) and Hsp90 (HtpG), assist protein folding by either promoting the "forward" folding or preventing the aggregation of proteins. However, once aggregates have formed, these molecular chaperones cannot facilitate protein disaggregation.
Hsp104 (ClpB) is a 600 kDa ATP-dependent molecular machine that, together with the cognate Hsp70 chaperone system, has the remarkable ability to rescue stress-damaged proteins from a previously aggregated state. Dr. Tsai's lab is interested in understanding how ClpB converts the energy derived from ATP binding and/or hydrolysis into mechanical work in order to disaggregate previously aggregated proteins. To this end, they have solved the atomic structure of ClpB using X-ray crystallography, and the structure of the functional ClpB assembly using electron cryo-microscopy and single-particle reconstruction techniques (Lee et al. Cell 2003). More recently, they have determined the hexameric structures of ClpB in different nucleotide-bound states, which revealed the conformational changes that occur during ATP binding and hydrolysis (Lee et al. Mol. Cell 2007). Taken together, their structure provides the much needed stereochemical framework to further investigate the mechanism of protein disaggregation (e.g. Weibezahn et al. Cell 2004; Haslberger et al. Mol. Cell 2007).
In recognition of the Tsai Lab's structural and mechanistic studies of ClpB, Dr. Tsai was awarded The Welch Foundation's 2008 Norman Hackerman Award in Chemical Research. This prestigious award is given to encourage and recognize young chemical scientists in Texas for their past research endeavors, and to serve as encouragement to those who are embarking on careers dedicated to increasing our fundamental understanding of chemistry.
- Lee J, Kim JH, Biter AB, Sielaff B, Lee S and Tsai FT. Heat shock protein (Hsp 70) is an activator of the Hsp104 motor. Proc Natl Acad Sci USA, 110(21):8513-8 (2013). PubMed
- Biter AB, Lee S, Sung N and Tsai FT. Structural basis for intersubunit signaling in a protein disaggregating machine. Proct Natl Acad Sci USA, 109(31):12515-20 (2013). PubMed
- Biter AB, Lee J, Sung N, Tsai FT and Lee S. Functional Analysis of Conserved Cis- and Trans-elements in Hsp104 Protein Disaggregating Machine. J Struct Biol, 179(2):172-80 (2012). PubMed
- Lee S, Augustin S, Tatsuta T, Gerdes F, Langer T and Tsai FT. Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease. J Biol Chem, 286(6):4404-11 (2011). PubMed
- Sielaff B, Lee KS and Tsai FT. Structural and Functional Conservation of Mycobacterium tuberculosis GroEL Paralogs Suggests that GroEl1 is a Chaperonin. J Mol Biol, 405:831-839 (2011). PubMed
- Lee S, Sielaff B, Lee J and Tsai FT. CryoEM Structure of Hsp104 and Its Mechanistic Implication for Protein Disaggregation. Proc Natl Acad Sci USA, 107:8135-8140 (2010). PubMed
- Sielaff B and Tsai FT. T M-domain controls Hsp104 protein remodeling activity in an Hsp70/Hsp40-dependent manner. J Mol Biol, 402(1):30-7 (2010). PubMed
For more publications, see listing on PubMed.
Department: Biochemistry and Molecular Biology
Address: Baylor College of Medicine
One Baylor Plaza,
Houston, TX 77030
Additional Links: Tsai Lab, Biochemistry