Christopher W. Akey, Ph.D.

William J. Lehman, Ph.D.

Professor of Physiology & Biophysics

B.S. University of Richmond
Ph.D. Cornell University

Phone: (617) 358-8451
Fax: (617) 358-8804
Address: see below
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We are studying the structure and function of macromolecular machines and chaperones. In our work, we use biochemistry and molecular biology coupled with structural electron microscopy, X-ray crystallography and molecular modeling. This hybrid approach allows us to create snapshots of these large assemblies and thus, to infer function from form.

Drosophila apoptosome

The apoptosome and other signaling platforms

In the intrinsic death pathway, cytochrome c binds to Apaf-1 and triggers apoptosome assembly in the presence of dATP. This platform binds procaspase-9, which activates procaspase-3 and other downstream procaspases. To understand this process, we determined a structure of the human apoptosome at 12.8Å resolution and created a model of this heptameric platform, which contains 49 domains and 7 cytochrome c molecules. Higher resolution studies of the active apoptosome should provide additional insights into the assembly and function of this cell killer. In parallel studies, we are determining structures of the Drosophila Apaf-1 related killer (Dark) and of other signaling platforms that mediate inflammatory responses to bacteria.

Ribosome-channel complexes

Nascent secretory proteins are translocated into the lumen of the ER. Conversely, membrane proteins are gated laterally into the lipid bilayer from the channel. We seek to create a model of the co-translational translocon to understand these processes. Thus, we have determined the structure of native ribosome-channel complexes. We have further refined the structure of the canine ribosome to ~8.0Å resolution and created a complete homology model of the mammalian ribosome. Current studies are now targeting translocation factors such as the translocon associated protein complex (TRAP) and the oligosacharryl transferase (OST). Finally, we are also studying the bacterial ribosome-channel complex to provide additional insights into translocation.

Histone chaperones

Histones must be chaperoned when they are not associated with DNA. However, little is known about this process. Nucleoplasmin-like chaperones form pentamers which may associate to form decamers when they bind histone tetramers or octamers. Current studies are aimed at obtaining structures of chaperones with their cognate histones to decipher the mechanism of binding.

The Type IVb secretion system of Legionella pneumophila

The T4bSS forms a channel that translocates bacterial proteins into the host eukaryotic cell. This process is required for infectivity by Legionella, a facultative pathogen. When alveolar macrophages are infected, this leads to a severe pneumonia (Legionnaires’ disease), which is particularly deadly in hospitals. We are studying the T4bSS with the goal of creating a molecular model of its function. As a first step, we determined the crystal structure of the interacting domains of IcmR-IcmQ (Rm-Qn). IcmR is a chaperone that prevents IcmQ from inserting into membranes. IcmQ may then form extensive links between membranes to help assemble or stabilize the T4bSS. We are now focusing on other components of this protein translocase.
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Selected Publications:

Platonova, O., Akey, I.V., Head, J.F. and Akey, C.W. (2011). Crystal structure and function of human nucleoplasmin (Npm2): a histone chaperone in oocytes and early embryos. Biochemistry 50, 8078-8089.

Yuan, S., Yu, X., Asara, J.M., Heuser, J.E., Ludtke, S.J. and Akey, C.W. (2011). The holo-apoptosome: activation of procaspase-9 and interactions with procaspase-3. Structure 19, 1084-1096.

Yuan, S., Yu, X., Topf, M., Dorstyn L., Kumar, S., Ludtke, S.J. and Akey, C.W. (2011). Structure of the Drosophila apoptosome at 6.9Å resolution. Structure 19, 128-140.

Yuan, S., Yu, X., Topf, M., Ludtke, S.J., Wang, X. and Akey, C.W. (2010). Structure of an apoptosome procaspase-9 CARD complex. Structure 18, 571-583.

Raychaudhury, S., Farelli, J., Montminy T.P., Ménétret, J.F., Matthews, M., Roy, C.R., Head, J.F., Isberg, R.R. and Akey, C.W. (2009). The structure and function of interacting domains of IcmR-IcmQ from the Type IVb secretion system of Legionella pneumophila. Structure 17, 590-601.

Ménétret, J. F., Hegde, R.S., Woong, K., Gygi, S.P., Rapoport, T. A., and Akey, C.W. (2008). Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosome. Structure 16, 1126-1137.

Chandramouli, P., Topf, M., Ménétret, J.F., Eswar, N., Gutell, R.R., Sali, A., and Akey, C.W. (2008). Structure of the mammalian 80S ribosome at 8.7Å resolution. Structure 16, 535-548.

Ménétret, J.F., Schaletsky, J., Clemons, W.M. Jr., Osborne, A.R., Skanland, S., Denison, C., Gygi, S.P., Kirkpatrick, D.S., Park, E., Ludtke, S.J., Rapoport, T.A. and Akey, C.W. (2007). Ribosome binding of a single copy of the SecY complex: implications for protein translocation. Molec. Cell 28, 1083-1092.

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Contact Us

Department of Physiology and Biophysics
Boston University School of Medicine
700 Albany Street
Boston MA 02118-2526
Phone:(617) 358-8451
Fax: (617) 358-8804