Structural Basis for Target Protein Recognition by the Protein Disulfide Reductase Thioredoxin

Kenji Maeda; Per Hägglund; Christine Finnie; Birte Svensson; Anette Henriksen

doi:10.1016/j.str.2006.09.012

Structural Basis for Target Protein Recognition by the Protein Disulfide Reductase Thioredoxin

Kenji Maeda
, Per Hägglund
, Christine Finnie
, Birte Svensson^*
, Anette Henriksen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley α-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.

Originalsprog	Engelsk
Tidsskrift	Structure
Vol/bind	14
Udgave nummer	11
Sider (fra-til)	1701-1710
Antal sider	10
ISSN	0969-2126
DOI	https://doi.org/10.1016/j.str.2006.09.012
Status	Udgivet - 2006
Udgivet eksternt	Ja

Finansiering

Mette Therese Christensen and Karina Rasmussen are acknowledged for technical assistance. Anne Blicher is thanked for performing amino acid analysis. Jakob R. Winther (Copenhagen University) is gratefully thanked for helpful discussions. The Danish Technical Research Council (STVF, grant 26-03-0194) and the Carlsberg Foundation are acknowledged for financial support to B.S. C.F. receives a grant as a young research leader (grant 23-03-0073) from the Danish Agricultural and Veterinary Research Council (SJVF). K.M. holds a Ph.D. scholarship from the Technical University of Denmark.

Adgang til dokumentet

10.1016/j.str.2006.09.012

Biblioteksadgang?

Tjek tilgængelighed hos det Kgl. Bibliotek

Citationsformater

@article{0bc9469fba114ce0b4da4acd1dcdf886,

title = "Structural Basis for Target Protein Recognition by the Protein Disulfide Reductase Thioredoxin",

abstract = "Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley α-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.",

keywords = "PROTEINS",

author = "Kenji Maeda and Per H{\"a}gglund and Christine Finnie and Birte Svensson and Anette Henriksen",

year = "2006",

doi = "10.1016/j.str.2006.09.012",

language = "English",

volume = "14",

pages = "1701--1710",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "11",

}

TY - JOUR

T1 - Structural Basis for Target Protein Recognition by the Protein Disulfide Reductase Thioredoxin

AU - Maeda, Kenji

AU - Hägglund, Per

AU - Finnie, Christine

AU - Svensson, Birte

AU - Henriksen, Anette

PY - 2006

Y1 - 2006

N2 - Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley α-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.

AB - Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley α-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.

KW - PROTEINS

U2 - 10.1016/j.str.2006.09.012

DO - 10.1016/j.str.2006.09.012

M3 - Journal article

C2 - 17098195

AN - SCOPUS:33846393586

SN - 0969-2126

VL - 14

SP - 1701

EP - 1710

JO - Structure

JF - Structure

IS - 11

ER -