Summary for 4G55
| Entry DOI | 10.2210/pdb4g55/pdb |
| Related | 2XZG |
| Descriptor | Clathrin heavy chain 1, DIMETHYL SULFOXIDE, ACETATE ION, ... (7 entities in total) |
| Functional Keywords | beta-propeller, endocytosis |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side: Q00610 |
| Total number of polymer chains | 1 |
| Total formula weight | 42728.82 |
| Authors | Bulut, H.,Von Kleist, L.,Saenger, W.,Haucke, V. (deposition date: 2012-07-17, release date: 2012-08-01, Last modification date: 2024-02-28) |
| Primary citation | von Kleist, L.,Stahlschmidt, W.,Bulut, H.,Gromova, K.,Puchkov, D.,Robertson, M.J.,MacGregor, K.A.,Tomilin, N.,Tomlin, N.,Pechstein, A.,Chau, N.,Chircop, M.,Sakoff, J.,von Kries, J.P.,Saenger, W.,Krausslich, H.G.,Shupliakov, O.,Robinson, P.J.,McCluskey, A.,Haucke, V. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell(Cambridge,Mass.), 146:471-484, 2011 Cited by PubMed Abstract: Clathrin-mediated endocytosis (CME) regulates many cell physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. Within the endocytic network, clathrin functions as a central organizing platform for coated pit assembly and dissociation via its terminal domain (TD). We report the design and synthesis of two compounds named pitstops that selectively block endocytic ligand association with the clathrin TD as confirmed by X-ray crystallography. Pitstop-induced inhibition of clathrin TD function acutely interferes with receptor-mediated endocytosis, entry of HIV, and synaptic vesicle recycling. Endocytosis inhibition is caused by a dramatic increase in the lifetimes of clathrin coat components, including FCHo, clathrin, and dynamin, suggesting that the clathrin TD regulates coated pit dynamics. Pitstops provide new tools to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry and as modulators of cell signaling. PubMed: 21816279DOI: 10.1016/j.cell.2011.06.025 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.69 Å) |
Structure validation
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