BARBARA M. F. PEARSE

Curriculum Vitae

Publications


Current Research on the Endocytic Cycle

 

The clathrin coat at 21Å resolution

The clathrin terminal domains can be seen through the hexagonal and pentagonal windows. They form an inner polyhedral shell in contact with AP2 adaptors.

Barbara with her current collaborators who are responsible for the new map

Corinne Smith - presently working with clathrin cages to get as high a resolution as possible. She is now with Helen Saibil at Birkbeck College London. She has won an MRC career development award to explore further aspects of the clathrin cage assembly.

Lin Zhang - helping develop new assays for clathrin coat assembly and disassembly.

Niko Grigorieff - taking up a new position in January 1999 as Assistant Professor at Brandeis University.

We are pleased because we have succeeded in getting a new map of a clathrin coat in an aqueous environment. However, there is much more work to be done. The next step is to dock domain atomic structures into the EM map which preferably should be at a still higher resolution. Andrea Musacchio has kindly sent Corinne the coordinates of the atomic structure of the clathrin N-terminal domain (from the work of Ernst ter Haar and Tomas Kirchhausen, Harvard Medical School) and Andrea himself and Stephen Harrison (Howard Hughes Medical Institute and Children's Hospital, Laboratory of Molecular Medicine, Boston).

January 12th 1999. Alan Roseman, Corinne Smith, Barbara Pearse and Andrea Musacchio on the occasion when Andrea visited the lab to see how Corinne, with Alan's advice, had fitted the x-ray structure of the clathrin N-terminal domain into the EM map. Andrea gave an MRC Molecular Biology seminar outlining how he had constructed a model of the clathrin cage from three individual independent triskelions whose legs had been traced in the EM map. Putting all the results together is proving most informative.

July 20th 1999. Combining the information from electron cryomicroscopy and x-ray crystallography gives new insight into the biological function and mechanism of the clathrin assembly. It puts the stained glass into the windows. (Musacchio, A., Smith, C.J., Roseman, A.N., Harrison, S.C., Kirchhausen, T. and Pearse, B.M.F. Molecular Cell, 3, 761-770 (1999).

 

 

Tomas Kirchhausen has had a movie created which shows schematically how the triskelions may assemble and come apart.

 

Schematic drawing of a slice through a coat vesicle to show how receptors in the membrane may be coupled via adaptor molecules to the outer clathrin lattice.

 

The main part of the clathrin polyhedral cage is red with the alpha zigzag linker and the beta propeller of the terminal domain projecting toward the membrane. Receptors in the membrane contact adaptor proteins, which in turn interact with clathrin terminal domains.

Members of the family of nonvisual arrestins serve as adaptors for a number of seven transmembrane-helix proteins such as the beta 2 adrenergic receptor. AP-2 complexes serve as adaptors for growth-factor receptors, transferrin receptors, mannose-6-phosphate receptor and many others.


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Last updated 21 September 2000