Yong Yao's Research Focus
Dr. Yao’s research centers on using NMR spectroscopy as the primary tool to study 3D structures of biomolecules especially membrane proteins, aiming to understand how they function at or near biological membranes to maintain human health or elicit human disease. The goal is to provide novel molecular insights that can advance translational studies and drug development.
Yong Yao's Research Report
Molecular mechanism of BCL-2 mediated apoptosis Bcl-2 family proteins are regulators of apoptosis and key targets for drug discovery. Their interactions on the mitochondrian outer membrane result in membrane destruction and commit cells to apoptosis. However, the molecular basis for these complex network of interactions in the context of membrane remains elusive. Recently I have developed methods to for generating tail anchored BCL-XL, a dominant inhibitor of apoptosis, to lipid bilayer membranes. This has allowed me to perform parallel functional and NMR studies, and to describe the first atomic view of a membrane-inserted BCL-2 family protein. This work is very exciting and has generated a substantial interest in the field. I plan to apply this technique to generate membrane embedded BAX, the key pro-death apoptotic protein, and study its structure and interaction with membrane integrated BCL-XL. This study will be very important and of high impact because (1) it will provide the first structure of membrane embedded BAX protein; (2) it will provide the first structure of a heterodimer complex between pro-survival and pro-death proteins in membranes; (3) the atomic structure of membrane integrated BAX protein and the molecular interactions between BCL-XL and BAX will shed light on mechanism of how BCL-2 proteins modulate apoptosis and provide insights to new anti-cancer drug development. Solid-state NMR spectroscopy of membrane proteins in membrane environment Membrane proteins are major targets for biomedical research and drug discovery. Structure determination is the prerequisite step for these efforts. Solid state NMR spectroscopy has a unique position in the field of structure biology of membrane proteins because it has the ability to determine the structures of membrane proteins in their native membrane environments and at the same time, probe protein dynamics, which is important to its function. My keen interest focuses on developing methods to generate membrane protein samples which are both biological active and amenable to high resolution NMR spectroscopy, and to determine membrane protein structures in their near native environments. Recently I have used a b-barrel outer membrane protein Ail, a key virulent factor from Yersinia pestis, as an example to demonstrate for the first time, high resolution solid state NMR spectroscopy and biologic activity assay can be obtained with the same sample where Ail is reconstituted into lipid bilayer membranes. On basis of this important research, I plan to (1) build up the membrane complexity by including LPS (lipopolysaccharide), a major component of the bacterium outer membrane, into the membrane composition, and study the effects of LPS on Ail’s structure and dynamics, (2) continue to develop methods to extract structural constraints from solid state NMR experiments and get high resolution 3D structure of Ail in membranes, and (3) elucidate the molecular interactions of Ail and its human host ligands such as vitronectin. This research is very important because it will provide the first b-barrel outer membrane protein structure determined in physiological membranes by solid state NMR method and will advance our understanding of how bacterial pathogens interacting with human host.
Yong Yao's Bio
Education and Training
B.Sc. Chemistry, Nanjing University, Nanjing, China. 1998
Ph.D. Chemistry, Nanjing University, Nanjing, China. Advisor: Wenxia Tang. 2003
Postdoctoral, The Scripps Research Institute, La Jolla, CA. Advisor: Jane Dyson. 2003 - 2006
Postdoctoral, Sanford Burnham Prebys Medical Discovery Institute (SBP), La Jolla, CA. Advisor: Francesca Marassi. 2006 - 2009
Professional experience and Professional Activities
Staff Scientist, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA. 2009 – present
Member, American Chemical Society 2006 – 2010
Member, Biophysical Society 2007 - present
Winter School on Biomolecular Solid-state NMR, Stowe, VT 2010
Honors and Awards
Reming Scholarship, Nanjing, China. 1995
Outstanding Graduate Award, Nanjing University, Nanjing, China. 2000
Outstanding Graduate Award, Nanjing University, Nanjing, China. 2001
Keystone Symposia Scholarship, Frontiers in Structure Biology. 2006
- Qian C, Yao Y, Wu Y, Tang W (2000) Kinetic studies of imidazole and its methyl derivative binding to metmyoglobin: effects of substitute methyl on the binding affinity. Biometals 13, 267-272.
- Wei H, Luo X, Wu Y, Yao Y, Guo Z, Longgen Z (2000) Compositions and conformations of several transition metal complexes with a nonapeptide hormone oxytocin. Journal of the Chemical Society, Dalton Transactions, 4196-4200.
- Yao Y, Ju HX, Wu YB, Yang SJ, Tang WX (2000) Electrochemical study on the alkaline isomerization of cytochrome c and ligand-binding cytochrome c in the presence of pyridine and 2-methyl-pyridine. Chinese Journal of Inorganic Chemistry 16, 346-352.
- Yao Y, Wu Y, Qian C, Tang W (2000) NMR studies of 4-methylimidazole binding to cytochrome c: effects of methyl substituent on the binding affinity, the orientation of the ligand plane, and the electronic structure of the heme. Journal of the Chemical Society, Dalton Transactions, 4069-4074. January 22, 2018 CURRICULUM VITAE - Yong YAO, Ph.D. Page 2 of 6
- Banci L, Bertini I, Liu G, Lu J, Reddig T, Tang W, Wu Y, Yao Y, Zhu D (2001) Effects of extrinsic imidazole ligation on the molecular and electronic structure of cytochrome c. J Biol Inorg Chem 6, 628-637.
- Qian C, Yao Y, Ye K, Wang J, Tang W, Wang Y, Wang W, Lu J, Xie Y, Huang Z (2001) Effects of charged amino-acid mutation on the solution structure of cytochrome b(5) and binding between cytochrome b(5) and cytochrome c. Protein Sci. 10, 2451-2459. (PMCID: 2374031).
- Wu YB, Lu J, Yao Y, Bai ZP, Tang WX, Zhu DX, Banci L, Bertini I, Liu G, Reddig T (2001) Solution structure of the imidazole complex of cytochrome c. Chemical Journal of Chinese Universities 22, 947-948.
- Yao Y, Qian C, Wu Y, Hu J, Tang W (2001) 1H NMR study of 2-methylimidazole binding to cytochrome c: a comprehensive investigation of the role of the methyl substituent on the ligand binding affinity and heme electronic structure in imidazole–cytochrome c complexes. Journal of the Chemical Society, Dalton Transactions, 1841-1845.
- Qian CM, Wang YH, Wang WH, Yao Y, Hu J, Lu JX, Xie Y, Huang ZX, Tang WX (2002) Effects of surface negatively charged amino acid mutation on binding between Cytochrome b5 and Cytochrome c. Chemical Journal of Chinese Universities 23, 1294-1298.
- Yao Y, Qian C, Ye K, Wang J, Bai Z, Tang W (2002) Solution structure of cyanoferricytochrome c: ligand-controlled conformational flexibility and electronic structure of the heme moiety. J Biol Inorg Chem 7, 539-547.
- Qian C, Yao Y, Tong Y, Wang J, Tang W (2003) Structural analysis of zinc-substituted cytochrome c. J Biol Inorg Chem 8, 394-400.
- Yao Y, Tang W (2003) NMR investigation of the alkaline-like conformational transition of horse heart cytochrome c in the presence of exogenous thiazole. Biophys. Chem. 104, 459-468.
- Yao Y, Wu Y, Qian C, Ye K, Wang J, Tang W (2003) NMR study of the conformational transition of cytochrome c upon the displacement of Met80 by exogenous ligand: structural and magnetic characterization of azidoferricytochrome c. Biophys. Chem. 103, 13-23.
- Huang J, Yao Y, Lin J, Ye YH, Sun WY, Tang Dagger WX (2004) The solution structure of rat Abeta-(1-28) and its interaction with zinc ion: insights into the scarcity of amyloid deposition in aged rat brain. J Biol Inorg Chem 9, 627-635.
- Yao Y, Martinez-Yamout MA, Dyson HJ (2005) Backbone and side chain 1H, 13C and 15N assignments for Escherichia coli SdiA1-171, the autoinducer-binding domain of a quorum sensing protein. J. Biomol. NMR 31, 373-374.
- Yao Y, Martinez-Yamout MA, Dickerson TJ, Brogan AP, Wright PE, Dyson HJ (2006) Structure of the Escherichia coli quorum sensing protein SdiA: activation of the folding switch by acyl homoserine lactones. J. Mol. Biol. 355, 262-273.
- Yao Y, Dickerson TJ, Hixon MS, Dyson HJ (2007) NMR detection of adventitious xylose binding to the quorum-sensing protein SdiA of Escherichia coli. Bioorg. Med. Chem. Lett. 17, 6202-6205. (PMCID: 2249169).
- Yao Y, Bhabha G, Kroon G, Landes M, Dyson HJ (2008) Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution. J. Biomol. NMR 40, 23-30.
- Yao Y, Bobkov AA, Plesniak LA, Marassi FM (2009) Mapping the interaction of pro-apoptotic tBID with pro-survival BCL-XL. Biochemistry 48, 8704-8711. (PMCID: 2762941).
- Plesniak LA, Salzameda B, Hinderberger H, Regan E, Kahn J, Mills SA, Teriete P, Yao Y, Jennings P, Marassi F, Adams JA (2010) Structure and Activity of CPNGRC: A Modified CD13/APN Peptidic Homing Motif. Chem. Biol. Drug Des. 75, 551-562. (PMCID: 2890305).
- Teriete P, Yao Y, Kolodzik A, Yu J, Song H, Niederweis M, Marassi FM (2010) Mycobacterium tuberculosis Rv0899 adopts a mixed alpha/beta-structure and does not form a transmembrane beta-barrel. Biochemistry 49, 2768-2777. (PMCID: 2847638).
- Yao Y, Barghava N, Kim J, Niederweis M, Marassi FM (2012) Molecular Structure and Peptidoglycan Recognition of Mycobacterium tuberculosis ArfA (Rv0899). J. Mol. Biol. 416, 208-220. (PMCID: 3269530).
- Ding Y, Fujimoto LM, Yao Y, Marassi FM (2015) Solid-state NMR of the Yersinia pestis outer membrane protein Ail in lipid bilayer nanodiscs sedimented by ultracentrifugation. J. Biomol. NMR 61, 275-286. (PMCID: PMC4398618).
- Ding Y, Fujimoto LM, Yao Y, Plano GV, Marassi FM (2015) Influence of the lipid membrane environment on structure and activity of the outer membrane protein Ail from Yersinia pestis. Biochim. Biophys. Acta 1848, 712-720. (PMCID: PMC4281492).
- Gong XM, Ding Y, Yu J, Yao Y, Marassi FM (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim. Biophys. Acta 1848, 299-306. (PMCID: PMC4216782). Journal Cover.
- Marassi FM, Ding Y, Schwieters CD, Tian Y, Yao Y (2015) Backbone structure of Yersinia pestis Ail determined in micelles by NMR-restrained simulated annealing with implicit membrane solvation. J. Biomol. NMR 63, 59-65. (PMCID: PMC4577439).
- Yao Y, Fujimoto LM, Hirshman N, Bobkov AA, Antignani A, Youle RJ, Marassi FM (2015) Conformation of BCL-XL upon Membrane Integration. J. Mol. Biol. 427, 2262-2270. (PMCID: PMC4457587).
- Godoi PH, Wilkie-Grantham RP, Hishiki A, Sano R, Matsuzawa Y, Yanagi H, Munte CE, Chen Y, Yao Y, Marassi FM, Kalbitzer HR, Matsuzawa S, Reed JC (2016) Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Antiapoptotic B Cell Lymphoma Gene 2 Family Proteins. J. Biol. Chem. 291, 14072-14084. (PMCID: 4933167).
- Yao Y, Nisan D, Fujimoto LM, Antignani A, Barnes A, Tjandra N, Youle RJ, Marassi FM (2016) Characterization of the membrane-inserted C-terminus of cytoprotective BCL-XL. Protein Expr. Purif. 122, 56-63. (PMCID: 4842142).
- Dutta SK, Yao Y, Marassi FM (2017) Structural Insights into the Yersinia pestis Outer Membrane Protein Ail in Lipid Bilayers. J Phys Chem B 121, 7561-7570. (PMCID: In process).
- Yao Y, Dutta SK, Park SH, Rai R, Fujimoto LM, Bobkov AA, Opella SJ, Marassi FM (2017) High resolution solid-state NMR spectroscopy of the Yersinia pestis outer membrane protein Ail in lipid membranes. J. Biomol. NMR 67, 179-190. (PMCID: In process).
- Ekanayake V, Nisan D, Ryzhov P, Yao Y, Marassi FM (2018) tBID forms soluble lipoprotein particles that bind cytoprotective BCL-XL. J Biol Chem. Submitted.
- Viacava Follis A, Llambi F, Kalkavan H, Yao Y, Phillips AH, Park CG, Marassi FM, Green DR, Kriwacki RW (2018) Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nature Chemical Biology In press.