Career Opportunities in the Akey Lab
For additional information please contact:
Dr. Christopher W. Akey
Professor of Physiology and Biophysics
Email: cakey@bu.edu
Visit my website!
A postdoctoral position is available in the Akey lab to study histone chaperones, ER and bacterial translocation channels, membrane proteins and caspase activation platforms (apoptosomes, inflammasomes). These projects use X-ray crystallography and electron cryo-microscopy. One or two positions are available, and will be filled based on the background and ability of the applicants. One position is available on an NIH training grant that requires the postdoctoral candidate to be a US citizen or hold a Green card. Candidates should provide a CV and a list of references, along with an email address and phone number for each reference.
We have complete facilities available for high resolution structure determination which include: a 200 kV Tecnai F20 microscope with Field emission gun, an RAXIS IV++ equipped with Osmic focusing mirrors, and an older RAXIS II system. Both crystallographic stations are cooled with Xstream cryo-systems. Computing is provided by ~13 SGIs and a Linux cluster with 32 cpus.
Histone chaperones
We are studying specialized histone chaperones that store histones and in some cases, transfer them to DNA to form nucleosomes. These chaperones are members of the Nucleoplasmin (Np) and N1 families. In a proteomics approach, six crystal structures have been determined from five Np family members. Moreover, work is progressing on domains that bind to DNA and function in nucleolar targeting, as well as domains of N1, a tetramer specific chaperone. We are currently developing approaches to co-crystallize these chaperones with their cognate histones. This work is funded by an RO1 from the NIH.
Relevant Papers
Namboodiri, H.V.M., Schmidt-Zachmann, M.S., Akey, I.V., Head, J.F. & Akey, C.W. (submitted). Structure and function of Xenopus NO38-core, a histone chaperone in the nucleolus.
Namboodiri, H.V.M., Dutta, S., Akey, I.V., Head, J.F. & Akey, C.W. (2003). The crystal structure of Drosophila NLP-core provides insight into pentamer formation and histone binding. Structure 11,175-86.
Akey, C.W. & Luger, K. (2003). Histone chaperones and nucleosome assembly. Curr. Opin. Struct. Biol.13, 6-14.
Dutta, S., Akey, I.V., Dingwall, C., Hartman, K.L., Laue, T., Nolte, R.T., Head, J.F. & Akey, C.W. (2001). The crystal structure of nucleoplasmin-core: Implications for histone binding and nucleosome assembly. Molec. Cell 8, 841-853.
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The ribosome-channel complex of the ER
The ribosome-channel complex translocates nascent secretory proteins into the ER lumen and participates in the topogenesis of all membrane proteins. We are determining the structure of the mammalian translocon and its component parts (total mass ~4.4 MDa). In this work, membrane proteins and soluble domains are being expressed, crystallized and studied by X-ray crystallography. Positions of the various components in the translocon and the structure of the channel and ribosome are being determined by single-particle electron cryo-microscopy, at resolutions that reveal alpha helices. By bringing together these structures, we will provide a model of this protein biogenesis machine. This project is supported by an RO1 from NIH.
Relevant Papers
Ménétret, J. F., Hegde, R.S., Heinrich S., Ludtke, S., Rapoport, T. A., & Akey, C. W. (submitted). Architecture of the ribosome-channel complex derived from native membranes.
Morgan, D. G., Ménétret, J. F., Neuhof, A., Rapoport, T. A., & Akey, C. W. (2002). Structure of the mammalian ribosome-channel complex at 17Å resolution. J. Mol. Biol. 324, 871-886.
Ménétret, J. F., Neuhof, A., Morgan, D. G., Plath, K., Rademacher, M., Rapoport, T. A., & Akey, C. W. (2000). The structure of ribosome-channel complexes engaged in protein translocation. Molec. Cell 6, 1219-1232.
Morgan, D. G., Ménétret, J. F., Rademacher, M., Neuhof, A., Akey, I. V., Rapoport, T. A., & Akey, C. W. (2000). A comparison of the yeast and the rabbit 80S ribosome reveals the topology of the nascent chain exit tunnel, inter-subunit bridges and mammalian rRNA expansion segments. J. Mol. Biol. 301, 301-321.
Meyer, T.H., Ménétret, J.F., Breitling, R., Miller, K.R., Akey, C.W. & Rapoport, T.A. (1999) The bacterial SecY/E translocation complex forms channel-like structures similar to those of the eukaryotic Sec61p complex. J. Mol. Biol. 285, 1789-1800.
Hanein, D., Matlack, K. E.S., Jungnickel, B., Plath, K., Kalies, K-U., Miller, K.R., Rapoport, T.A. & Akey, C.W. (1996) Oligomeric rings of the Sec61p complex induced by ligands required for protein translocation. Cell 87, 721-732.
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Apoptosomes and other caspase activation platforms
Apaf1 and other related proteins that contain a dATP/ATP binding domain, oligomerize to form large, caspase activation platforms (~600-2,500 kDa). We are comparing structures of the human Apaf1 and Drosophila DARK apoptosomes, to reveal details of their function. We have also begun work on several other members of the NOD superfamily, which play critical roles in the inflammatory response pathway. This project is funded by an RO1 grant from the NIH.
Recent papers:
Acehan, D., Jiang, X., Morgan, D.G., Wang, X. & Akey, C.W. (2002). Three-dimensional structure of the apoptosome: Implications for assembly, procaspase-9 binding and activation. Molec. Cell 9, 423-432.
Protein translocation in Legionella pneumophila
Legionella is able to colonize eukaryotic cells after being eaten by phagocytosis. The bacterium then subverts the lysomal pathway and creates an ER-like compartment in which to replicate. This process in human lung macrophages may lead to severe pneumonia and death in immuno-compromised individuals. A critical phase of this infectious process involves the translocation of proteins into the host cell within the first 5 minutes of contact between the cells. We are studying the structure of two putative channels that may help create this protein translocation machine, using EM and X-ray crystallography. This work is a collaboration with the laboratories of Dr.Ralph Isberg (Tufts, HHMI) and Craig Roy (Yale).
For additional information please contact:
Dr. Christopher W. Akey
Professor of Physiology and Biophysics
Email: cakey@bu.edu
Visit my website!
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