5ELJ

Isoform-specific inhibition of SUMO-dependent protein-protein interactions

5ELJ の概要

• エントリーDOI: 10.2210/pdb5elj/pdb
• 分子名称: SUMO-Affirmer-S2D5, Small ubiquitin-related modifier 1 (3 entities in total)
• 機能のキーワード: ubiquitin, sumoylation, signaling protein
• 由来する生物種: synthetic construct; 詳細
• 細胞内の位置: Nucleus membrane: P63165
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22938.19

構造登録者

Hughes, D.J.,Tiede, C.,Hall, N.,Tang, A.A.S.,Trinh, C.H.,Zajac, K.,Mandal, U.,Howell, G.,Edwards, T.A.,McPherson, M.J.,Tomlinson, D.C.,Whitehouse, A. (登録日: 2015-11-04, 公開日: 2016-11-16, 最終更新日: 2024-01-10)

主引用文献

Hughes, D.J.,Tiede, C.,Penswick, N.,Tang, A.A.,Trinh, C.H.,Mandal, U.,Zajac, K.Z.,Gaule, T.,Howell, G.,Edwards, T.A.,Duan, J.,Feyfant, E.,McPherson, M.J.,Tomlinson, D.C.,Whitehouse, A.
Generation of specific inhibitors of SUMO-1- and SUMO-2/3-mediated protein-protein interactions using Affimer (Adhiron) technology.
Sci Signal, 10:-, 2017

PubMed Abstract: Because protein-protein interactions underpin most biological processes, developing tools that target them to understand their function or to inform the development of therapeutics is an important task. SUMOylation is the posttranslational covalent attachment of proteins in the SUMO family (SUMO-1, SUMO-2, or SUMO-3), and it regulates numerous cellular pathways. SUMOylated proteins are recognized by proteins with SUMO-interaction motifs (SIMs) that facilitate noncovalent interactions with SUMO. We describe the use of the Affimer system of peptide display for the rapid isolation of synthetic binding proteins that inhibit SUMO-dependent protein-protein interactions mediated by SIMs both in vitro and in cells. Crucially, these synthetic proteins did not prevent SUMO conjugation either in vitro or in cell-based systems, enabling the specific analysis of SUMO-mediated protein-protein interactions. Furthermore, through structural analysis and molecular modeling, we explored the molecular mechanisms that may underlie their specificity in interfering with either SUMO-1-mediated interactions or interactions mediated by either SUMO-2 or SUMO-3. Not only will these reagents enable investigation of the biological roles of SUMOylation, but the Affimer technology used to generate these synthetic binding proteins could also be exploited to design or validate reagents or therapeutics that target other protein-protein interactions.

PubMed: 29138295
DOI: 10.1126/scisignal.aaj2005

実験手法

X-RAY DIFFRACTION (1.983 Å)