Structural basis of cellular redox regulation by human TRP14

Rang Woo Joo, Jun Kim Seung, Woojin Jeong, Hea Cho Yoon, Chul Lee Sang, Je Chung Yong, Goo Rhee Sue, Eon Ryu Seong

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Thioredoxin-related protein 14 (TRP 14) is involved in regulating tumor necrosis factor-α-induced signaling pathways in a different manner from human thioredoxin 1 (Trx1). Here, we report the crystal structure of human TRP14 determined at 1.8-Å resolutions. The structure reveals a typical thioredoxin fold with characteristic structural features that account for the substrate specificity of the protein. The surface of TRP14 in the vicinity of the active site includes an extended loop and an additional α-helix, and the distribution of charged residues in the surface is different from Trx1. The distinctive dipeptide between the redox-active cysteines contributes to stabilizing the thiolate anion of the active site cysteine 43, increasing reactivity of the cysteine toward substrates. These structural differences in the active site suggest that TRP14 has evolved to regulate cellular redox signaling by recognizing a distinctive group of substrates that would complement the group of proteins regulated by Trx1.

Original languageEnglish
Pages (from-to)48120-48125
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number46
DOIs
StatePublished - 12 Nov 2004

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