Conformation switching of clathrin light chain regulates clathrin lattice assembly
| Autor: | Peter K. Hwang, Michael Lane, Benjamin D. Sellers, Robert J. Fletterick, Frances M. Brodsky, Jeremy D. Wilbur, Matthew P. Jacobson, Joel A. Ybe |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Macromolecular Substances Protein Conformation Endocytic cycle Molecular Sequence Data Static Electricity Coated vesicle Endocytosis Crystallography X-Ray Clathrin General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Protein structure Animals Humans Amino Acid Sequence Molecular Biology 030304 developmental biology Organelles 0303 health sciences biology Sequence Homology Amino Acid Vesicle Clathrin-Coated Vesicles Cell Biology Clathrin Light Chains Cell biology Protein Subunits biology.protein Clathrin adaptor proteins Cattle Sequence Alignment 030217 neurology & neurosurgery Developmental Biology Protein Binding |
| Popis: | Summary Clathrin-coated vesicle formation is responsible for membrane traffic to and from the endocytic pathway during receptor-mediated endocytosis and organelle biogenesis, influencing how cells relate to their environment. Generating these vesicles involves self-assembly of clathrin molecules into a latticed coat on membranes that recruits receptors and organizes protein machinery necessary for budding. Here we define a molecular mechanism regulating clathrin lattice formation by obtaining structural information from co-crystals of clathrin subunits. Low resolution X-ray diffraction data (7.9–9.0 A) was analyzed using a combination of molecular replacement with an energy-minimized model and noncrystallographic symmetry averaging. Resulting topological information revealed two conformations of the regulatory clathrin light chain bound to clathrin heavy chain. Based on protein domain positions, mutagenesis, and biochemical assays, we identify an electrostatic interaction between the clathrin subunits that allows the observed conformational variation in clathrin light chains to alter the conformation of the clathrin heavy chain and thereby regulates assembly. |
| Databáze: | OpenAIRE |
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