title: The structure of human tripeptidyl peptidase II as determined by a hybrid approach.
abstract: Tripeptidyl-peptidase II (TPPII) is a high molecular mass (∼5 MDa) serine protease, which is thought to act downstream of the 26S proteasome, cleaving peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has been determined to subnanometer resolution by cryoelectron microscopy and single-particle analysis. The complex is built from two strands forming a quasihelical structure harboring a complex system of inner cavities. HsTPPII particles exhibit some polymorphism resulting in complexes consisting of nine or of eight dimers per strand. To obtain deeper insights into the architecture and function of HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a comparative model of HsTPPII dimers and molecular dynamics flexible fitting. Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation.
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schönegge
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villa
authors.forename: Friedrich
authors.initials: F
authors.lastname: Förster
authors.forename: Reiner
authors.initials: R
authors.lastname: Hegerl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumeister
authors.forename: Beate
authors.initials: B
authors.lastname: Rockel
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020285:Cryoelectron Microscopy; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004926:Escherichia coli; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D008970:Molecular Weight; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D020035:Holoenzymes; D011994:Recombinant Proteins; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases