Assistant Professor
CIHR New Investigator
MSFHR Career Investigator
University of British Columbia, 2001, B.Sc.(Honours)
University of British Columbia, 2006, Ph.D.
Harvard Medical School, 2010, Postdoctoral Fellow
phone: 6048273976
fax: 6048225227
Lab Phone
phone: 6048274274
Life Sciences Centre Office 5301
2350 Health Sciences Mall
Vancouver, BC V6T 1Z3

**Postdoctoral fellow and graduate student positions available. Please contact Dr. Calvin Yip by e-mail.**

1. PIKK kinases and kinase complexes

Members of family of kinases are distinguished by their extraordinarily large size and a propensity to form even larger multi-protein assemblies. PIKK members play central roles in regulating cell growth and proliferation, responses to DNA damage and RNA splicing errors, and transcription activation. We use single particle EM, yeast genetics and other biochemical and structural approaches to address the fundamental question of why these kinases need to so large in size.

figure1a                                                                                                                   Figure 1. Members of the PIKK family

2. Autophagy machinery

Autophagy is an evolutionarily conserved pathway that encapsulates large objects to be degraded in a double-membrane vesicle called the autophagosome and targeting this cargo to the lysosome for breakdown. We are interested understanding how a specialized group of proteins called Atg proteins mediate the different steps of this important membrane trafficking and degradative pathway.

Figure1                                                                                    Figure 2. Schematic representation of the autophagy pathway

3. Single particle electron microscopy (EM)

Single particle EM has emerged as an indispensible tool to characterize the structures of large proteins and multi-protein assemblie. Because it does not involve crystallization, single particle EM has the capability to visualize different conformational states of dynamic proteins and protein complexes. We are interested in developing new methods and procedures to facilitate the analysis of dynamic proteins and macromolecular assemblies.

Figure5                                                                            Figure 3. (a) Raw image and (b) class averages of an Atg protein complex


Chew, L.H., Lu, S., Liu, X., Li, F.K., Yu, A.Y., Klionsky, D.J., Dong, M.Q., Yip, C.K. Molecular interactions of the Saccharomyces cerevisiae Atg1 complex provide insights into assembly and regulator mechanisms. (2015) Autophagy 11: 891-905.

Kerr, C.H., Wang, Q.S., Keatings, K., Khong, A., Allan, D., Yip, C.K., Foster, L.J., Jan, E. The 5′ untranslated region of a novel infectious molecular clone of the dicistrovirus cricket paralysis virus modulates infection. (2015) Journal of Virology 89: 5919-5934.

Setiaputra, D., Ross, J.D., Lu, S., Cheng, D.T., Dong, M.Q., Yip, C.K. Conformational flexibility and subunit arrangement of the modular yeast Spt-Ada-Gcn5 acetyltransferase complex. (2015) Journal of Biological Chemistry 290: 10057-10070.

Solomonson, M., Setiaputra, D., Makepeace, K.A., Lameignere, E., Petrotchenko, E.V., Conrady, D.G., Bergeron, J.R., Vuckovic, M., DiMaio, F., Borchers, C.H., Yip, C.K., Strynadka, N.C. Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism. (2015) Structure 23:571-583.

Chan, C.S., Song, X., Qazi, S.J., Setiaputra, D., Yip, C.K., Chao, T., Turner, R.J. Unusual pairing between assistants: Interaction of the twin-arginine system-specific chaperone DmsD with the chaperonin GroEL. (2015)  Biochemical and Biophysical Research Communications 456: 841-846.

Lamour, G., Yip, C.K., Li, H., Gsponer, J. High intrinsic mechanical flexibility of mouse prion nanofibrils revealed by measurements of axial and radial young’s moduli. (2014) ACS Nano 8: 3851-3861.

Chew, L.H., Yip, C.K. Structural biology of the macroautophagy machinery. (2014) Frontiers in Biology 9: 18-34.

Mao, K., Chew, L.H., Yip, C.K., Klionsky, D.J. The role of Atg29 phosphorylation in PAS assembly. (2013) Autophagy 9: 2178-2179.

Chew, L.H., Setiaputra, D., Klionsky, D.J., Yip, C.K. Structural characterization of the Saccharomyces cerevisiae autophagy regulatory complex Atg17-Atg31-Atg29. (2013) Autophagy 9: 1467-1474.

Mao, K., Chew, L.H., Inoue, Y., Cheong, H., Nair, U., Popelka, H., Yip, C.K., Klionsky, D.J. Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation. (2013) Proceedings of the National Academy of Sciences of the USA 110: E2875-E2884.

Chambers, M.G., Pyburn, T.M., Gonzalez-Rivera, C., Collier, S.E., Eli, I., Yip, C.K., Takizawa, Y., Lacy, D.B., Cover, T.L., Ohi, M.D. Structural analysis of the oligomeric states of Helicobacter pylori VacA toxin. (2013) Journal of Molecular Biology 425: 524-535.

Yip, C.K., Walz, T. Molecular structure and flexibility of the yeast coatomer as revealed by electron microscopy. (2011) Journal of Molecular Biology 408: 825-831.

Yip, C.K., Berscheminski, J., Walz, T. Molecular architecture of the TRAPPII complex and implications for vesicle tethering. (2010) Nature Structural & Molecular Biology 17: 1298-1304.

Lees, J.*, Yip, C.K.*, Walz, T., Hughson, F.M. Molecular organization of the COG vesicle tethering complex. (2010) Nature Structural & Molecular Biology 17: 1292-1297. *Authors contributed equally

Corbett, K.D., Yip, C.K., Ee, L., Walz, T., Amon, A., Harrison, S.C. The monopolin complex cross-links kinetochore compoments to regulate chromosome-microtubule attachments. (2010) Cell 142: 556-567.

Yip, C.K., Murata, K., Walz, T., Sabatini, D.M., Kang, S.A. (2010) Structure of the human mTOR Complex I and its implications for rapamycin inhibition. Molecular Cell 38: 768-774.

Ren, Y., Yip, C.K., Tripathi, A., Huie, D., Jeffrey, P.D., Walz, T., Hughson, F.M. (2009) A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1. Cell 139: 1119-1129.

Li, H., Motamedi, M.R., Yip, C.K., Wang, Z., Walz, T., Patel, D.J., Moazed, D. (2009) An alpha motif at Tas3C terminus mediates RITS cis spreading and promotes heterochromatic gene silencing. Molecular Cell 34: 155-167.

Wu, W., Sinha, D., Shikov, S., Yip, C.K., Walz, T., Billings, P.C., Lear, J.D., Walsh, P.N. (2008) Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa. Journal of Biological Chemistry 283: 18655-18664.