Yuan He Assistant Professor

Research Summary:

The He lab is interested in understanding the molecular mechanisms by which large, multi-subunit complexes engage in DNA-centric processes using cryo-electron microscopy (cryo-EM) and other biophysical and biochemical approaches. We focus on two main topics: (1) how eukaryotic gene transcription is regulated at different stages, and (2) how various types of DNA damage are repaired and why deficiencies in these repair pathways lead to pathology of cancer predisposition or accelerated aging.

Cryo-EM is a powerful tool well suited for revealing macromolecular assemblies’ structures at moderately high to near atomic resolution. It requires a considerably smaller amount of sample, is not limited by the size of the system of interest, and is well equipped for sorting conformational/biochemical heterogeneity in a single sample under close to physiological conditions. These advantages, together with ongoing technical breakthroughs (direct electron detector and phase plate), make cryo-EM a unique tool to further our structural understanding of complicated cellular processes.

Selected Publications:

Structural basis of transcription promoter opening using single particle cryo-EM. He Y, Yan C, Inouye C, Fang J, Tjian R, Ivanov I, and Nogales E. 2015; Manuscript in preparation.

Structural visualization of key steps in human transcription initiation. He Y, Fang J, Taatjes DJ, and Nogales E. Nature. 2013 March 28;495(7442.):481-486.

Structure of the 30-kDa Sin3-associated Protein (SAP30) in Complex with the Mammalian Sin3A Corepressor and Its Role in Nucleic Acid Binding. Xie T, He Y, Korkeamaki H, Zhang Y, Imhoff R, Lohi O, and Radhakrishnan I. Journal of Biological Chemistry. 2011 August 5;286(31):27814-27824.

Solution structure of a novel zinc finger motif in the SAP30 polypeptide of the Sin3 corepressor complex and its potential role in nucleic acid recognition. He Y, Imhoff R, Sahu A, and Radhakrishnan I. Nucleic Acids Research. 2009 April;37(7):2142-2152.

Solution NMR studies of apo-mSin3A and -mSin3B reveal that the PAH1 and PAH2 domains are structurally independent. He Y and Radhakrishnan I. Protein Science. 2008 January;17(1):171-175.

Structural Basis for Ubiquitin Recognition by SH3 Domains. He Y, Hicke L, and Radhakrishnan I. Journal of Molecular Biology. 2007 October 12;373(1):190-196.

Ubiquitin Binds to and Regulates a Subset of SH3 Domains. Stamenova SD, French ME, He Y, Francis SA, Kramer ZB, and Hicke L. Molecular Cell. 2007 January 26;25(2):273-284.

View all publications by Yuan He listed in the National Library of Medicine (PubMed).