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

doi:10.1016/j.str.2012.01.025

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

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Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	593-603
Number of pages	11
Journal	Structure
Volume	20
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2012.01.025
Publication status	Published - 4 Apr 2012
Externally published	Yes

Keywords

Aminopeptidases
Cryoelectron Microscopy
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Enzyme Activation
Escherichia coli
Holoenzymes
Humans
Molecular Dynamics Simulation
Molecular Weight
Protein Multimerization
Protein Structure, Secondary
Protein Structure, Tertiary
Recombinant Proteins
Serine Endopeptidases

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10.1016/j.str.2012.01.025

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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.",

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author = "Anne-Marie Sch{\"o}negge and Elizabeth Villa and Friedrich F{\"o}rster and Reiner Hegerl and J{\"u}rgen Peters and Wolfgang Baumeister and Beate Rockel",

year = "2012",

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doi = "10.1016/j.str.2012.01.025",

language = "English",

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T1 - The structure of human tripeptidyl peptidase II as determined by a hybrid approach

AU - Schönegge, Anne-Marie

AU - Villa, Elizabeth

AU - Förster, Friedrich

AU - Hegerl, Reiner

AU - Peters, Jürgen

AU - Baumeister, Wolfgang

AU - Rockel, Beate

PY - 2012/4/4

Y1 - 2012/4/4

N2 - 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.

AB - 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.

KW - Aminopeptidases

KW - Cryoelectron Microscopy

KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

KW - Enzyme Activation

KW - Escherichia coli

KW - Holoenzymes

KW - Humans

KW - Molecular Dynamics Simulation

KW - Molecular Weight

KW - Protein Multimerization

KW - Protein Structure, Secondary

KW - Protein Structure, Tertiary

KW - Recombinant Proteins

KW - Serine Endopeptidases

U2 - 10.1016/j.str.2012.01.025

DO - 10.1016/j.str.2012.01.025

M3 - Article

C2 - 22483107

SN - 0969-2126

VL - 20

SP - 593

EP - 603

JO - Structure

JF - Structure

IS - 4

ER -

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

Abstract

Keywords

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