Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly

• Yi Xing ^[1] ; Till Böcking ^[1] ; Matthias Wolf ^[1] ; Nikolaus Grigorieff ^[2] ; Tomas Kirchhausen ^[1] ; Stephen C Harrison ^[3]
  1. [1] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  2. [2] Howard Hughes Medical Institute

     Howard Hughes Medical Institute

     Estados Unidos

     
  3. [3] Department of Biological Chemistry and Molecular Pharmacology, Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 3, 2009, págs. 655-665
• Idioma: inglés
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  • The chaperone Hsc70 drives the clathrin assembly–disassembly cycle forward by stimulating dissociation of a clathrin lattice. A J-domain containing co-chaperone, auxilin, associates with a freshly budded clathrin-coated vesicle, or with an in vitro assembled clathrin coat, and recruits Hsc70 to its specific heavy-chain-binding site. We have determined by electron cryomicroscopy (cryoEM), at about 11 Å resolution, the structure of a clathrin coat (in the D6-barrel form) with specifically bound Hsc70 and auxilin. The Hsc70 binds a previously analysed site near the C-terminus of the heavy chain, with a stoichiometry of about one per three-fold vertex. Its binding is accompanied by a distortion of the clathrin lattice, detected by a change in the axial ratio of the D6 barrel. We propose that when Hsc70, recruited to a position close to its target by the auxilin J-domain, splits ATP, it clamps firmly onto its heavy-chain site and locks in place a transient fluctuation. Accumulation of the local strain thus imposed at multiple vertices can then lead to disassembly.