1995 B.S. in Biology. University of Science and Technology, China.
2002 Ph.D. in Biophysics. Johns Hopkins University School of Medicine. (Advisor: Dr. Cynthia Wolberger)
2002-05 Postdoc at University of California, Berkeley. (Advisor: Dr. Jennifer Doudna)
Research in my lab centers around the biology of RNA. In eukaryotic cells, stable RNAs are transcribed with a 3’ extension that is subsequently trimmed from 3’-to-5’, whereas aberrantly processed RNAs are subject to rapid degradation. A conserved 300 – 400 kDa exoribonuclease protein complex, the exosome, plays crucial roles in both the RNA 3’-end formation and turnover processes (Fig. 1). The nuclear exosome is required for the 3’ end formation of 5.8S rRNA, small nuclear and nucleolar RNAs; and involved in the degradation of inefficiently spliced and hyper– or hypo-adenylated pre-mRNAs. The cytoplasmic exosome is required for the degradation of normal mRNAs as well as those containing premature termination codons, lacking termination codons, or bearing AU-rich elements near the 3’ untranslated region. Using X-ray crystallography and biochemical tools, we aim to understand the architecture, working mechanism, and the regulation of this multi-subunit machinery.
Fig. 1. Exosome is a major player in RNA 3’-end formation and turnover.
RNA-protein (ribonucleoprotein) complexes, such as the ribosome, signal recognition particle (SRP), spliceosome, and telomerase, carry out essential functions inside cells. We are currently investigating the structural mechanism of SRP-mediated co-translational translocation of proteins across or into cell membranes. In this vital cellular process, SRP recognizes the hydrophobic signal sequence of the nascent polypeptide emerging from the ribosome, resulting in transient elongation arrest in eukaryotes, and targets the ribosome to the membrane via a GTP-dependent interaction with the SRP receptor (SR).
Fig. 2. SRP cycle in co-translational protein targeting.
Return to Top
Lu C, Ding F, Ke A. Crystal structure of the S. solfataricus archaeal exosome reveals conformational flexibility in the RNA-binding ring. Submitted.
Lu C, Smith AM, Fuchs RT, Ding F, Rajashankar K, Henkin TM, Ke A. Crystal structures of the SAM-III/SMK riboswitch reveal the SAM-dependent translation inhibition mechanism. Nature Structural & Molecular Biology. 2008 May;15:1076-1083
Wang HW, Wang J, Ding F, Callahan K, Bratkowski MA, Butler JS, Nogales E, Ke A. Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing. Proc Natl Acad Sci U S A. 2007 Oct 23;104:16844-16849.
Ke A, Ding F, Batchelor JD, Doudna JA. Structural roles of monovalent cations in the HDV ribozyme. Structure. 2007 Mar;15(3):281-7.
Wu S, Ke A, Doudna JA. A fast and efficient procedure to produce scFvs specific for large macromolecular complexes. J. Immunol Methods. 2007 Jan 10;318(1-2):95-101.
Spanggord RJ, Siu F, Ke A, Doudna JA. RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particle. Nat Struct Mol Biol. 2005 Dec;12(12):1116-22. Epub 2005 Nov 20.
Ke A, Doudna JA (2005), Catalytic strategies of self-cleaving ribozymes: Relics of an RNA world? The RNA World, 3rd Edition. (Book chapter)
Ke A, Doudna JA. Crystallization of RNA and RNA-protein complexes. Methods. 2004 Nov;34(3):408-14.
Ke A, Zhou K, Ding F, Cate JH, Doudna JA. A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature. 2004 May 13;429(6988):201-5.
Ke A, Wolberger C. Insights into binding cooperativity of MATa1/MATalpha2 from the crystal structure of a MATa1 homeodomain-maltose binding protein chimera. Protein Sci. 2003 Feb;12(2):306-12.
Ke A, Mathias JR, Vershon AK, Wolberger C. Structural and thermodynamic characterization of the DNA binding properties of a triple alanine mutant of MATalpha2. Structure. 2002 Jul;10(7):961-71.