title: Structural basis of cellular redox regulation by human TRP14.
abstract: Thioredoxin-related protein 14 (TRP14) is involved in regulating tumor necrosis factor-alpha-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-A 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 alpha-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.
authors.affiliation: Center for Cellular Switch Protein Structure and Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Euh-eun-dong, Yuseong-gu, Daejeon 305-806, Korea.
authors.forename: Joo Rang
authors.initials: JR
authors.lastname: Woo
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Woojin
authors.initials: W
authors.lastname: Jeong
authors.forename: Yoon Hea
authors.initials: YH
authors.lastname: Cho
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Yong Je
authors.initials: YJ
authors.lastname: Chung
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010121:Oxytocin / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; C491203:TXN protein, human; C482341:TXNDC17 protein, human; D010121:Oxytocin; D013879:Thioredoxins; D003545:Cysteine