title: Nuclear localization of clathrin involves a labile helix outside the trimerization domain.
abstract: Clathrin is a trimeric protein involved in receptor-mediated-endocytosis, but can function as a non-trimer outside of endocytosis. We have discovered that the subcellular distribution of a clathrin cysteine mutant we previously studied is altered and a proportion is also localized to nuclear spaces. MALS shows C1573A hub is a mixture of trimer-like and detrimerized molecules. The X-ray structure of the trimerization domain reveals that without light chains, a helix harboring cysteine-1573 is reoriented. We propose clathrin has a detrimerization switch, which suggests clathrin topology can be altered naturally for new functions.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, 212 S. Hawthorne Drive, Bloomington, IN 47405, USA. jybe@indiana.edu
authors.forename: Joel A
authors.initials: JA
authors.lastname: Ybe
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Fontaine
authors.forename: Todd
authors.initials: T
authors.lastname: Stone
authors.forename: Jay
authors.initials: J
authors.lastname: Nix
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lin
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mishra
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002966:Clathrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004705:Endocytosis / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012542:Scattering, Radiation
chemical_list: D002966:Clathrin; D050505:Mutant Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins