Stephen C. Harrison
Department of Biological Chemistry and Molecular Pharmacology
Department of Pediatrics (HMS)
Harvard Medical School
Seeley G. Mudd Bldg., Room 130
250 Longwood Ave.
Boston, MA 02115
Tel: (617) 432-5609
Fax: (617) 432-5600
Howard Hughes Medical Institute
Laboratory of Molecular Medicine
CLS, Room 3082
Children's Hospital
3 Blackfan Circle
Boston, MA 02115
Tel: (617) 355-7372
Fax: (617) 730-1967
Email: schadmin@crystal.harvard.edu
We are structural biologists concerned with the organization and dynamics of macromolecular assemblies. We ask the following kinds of questions: (1) How do viruses assemble and get into and out of cells? (2) How do clathrin-coated vesicles assemble, recruit cargo, bud off from their membrane of origin, and uncoat? (3) What is the molecular architecture of a kinetochore and how does this architecture embody its required mechanical and signal-transducing properties?
(1) We are particularly interested in determining the molecular events that accompany penetration of a virus into a cell – a process that takes the form of membrane fusion in the case of enveloped viruses and of membrane perforation in the case of non-enveloped viruses. Structural analyses of viruses and viral proteins are at the core of our efforts to understand these steps. Much of our recent work has focused on the double-strand RNA viruses and in particular on the proteins that carry out the membrane penetration step. Another component of our research seeks to extend our structural understanding of membrane fusion as facilitated by viral fusion proteins and to use the structural information to design screens for fusion inhibitors. (2) We are putting together a detailed molecular picture of a clathrin coated vesicle, by combining electron cryomicroscopy with x-ray crystallography. Recent progress includes an 8Å resolution reconstruction of a clathrin coat and a single-molecule analysis of Hsc70-driven uncoating. Longer range goals include analysis of dynamics: budding and uncoating. (Collaboration with the laboratories of Tomas Kirchhausen, IDI and Dept. of Cell Biology, Thomas Walz, Dept. of Cell Biology, and Niko Grigorieff, Brandeis). (3) The kinetochore of budding yeast is an assembly of at least 50 protein species. Together with the laboratory of Peter Sorger at MIT, we have undertaken to build up a three-dimensional picture of a yeast kinetochore, starting with efforts to crystallize some of its constituent protein complexes.
References: For a complete listing of publications on PubMed, click here.
BBS webpage updated 5/13/2010