title: The p41 fragment story.
abstract: The discovery of a fragment from the p41 form of invariant chain tightly bound to cathepsin L provided the first direct link between MHC class II molecules and the regulation of activity of lysosomal cysteine proteases. We recently determined the crystal structure of this p41 invariant chain fragment in complex with cathepsin L [EMBO J. 18, 793-803 (1999)]. This structure explains the specificity of the observed interactions and actually provides a tool, which can be utilized by means of molecular biology, to explore and understand the specificity of thyroglobulin type I domains and thus allow the design of specific inhibitors of papain-like cysteine proteases. The structure further supports the hypothesis that the thyroglobulin type I and II domains present in various proteins, sometimes in multiple repeats, are regulatory elements of the processing of these proteins by proteolytic cleavage.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia. dusan.turk@ijs.si
authors.forename: D
authors.initials: D
authors.lastname: Turk
authors.forename: G
authors.initials: G
authors.lastname: Guncar
authors.forename: V
authors.initials: V
authors.lastname: Turk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry* / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013954:Thyroglobulin / Q000737:chemistry
chemical_list: D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010446:Peptide Fragments; D013954:Thyroglobulin; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L