The structure of human tripeptidyl peptidase II as determined by a hybrid approach.

Anne-Marie Schönegge, Elizabeth Villa, Friedrich Förster, Reiner Hegerl, Jürgen Peters, Wolfgang Baumeister, Beate Rockel

Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Structure (London, England : 1993) 2012 Apr 4

filter terms:

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Anne-Marie Schönegge, Elizabeth Villa, Friedrich Förster, Reiner Hegerl, Jürgen Peters, Wolfgang Baumeister, Beate Rockel. The structure of human tripeptidyl peptidase II as determined by a hybrid approach. Structure (London, England : 1993). 2012 Apr 4;20(4):593-603