5V7Z

SSNMR Structure of the Human RIP1/RIP3 Necrosome

5V7Z の概要

• エントリーDOI: 10.2210/pdb5v7z/pdb
• NMR情報: BMRB: 30273
• 分子名称: PRO-LEU-VAL-ASN-ILE-TYR-ASN-CYS-SER-GLY-VAL-GLN-VAL-GLY-ASP, THR-ILE-TYR-ASN-SER-THR-GLY-ILE-GLN-ILE-GLY-ALA-TYR-ASN-TYR-MET-GLU-ILE (2 entities in total)
• 機能のキーワード: signaling complex, human functional amyloid, signaling protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 14516.15

構造登録者

Mompean, M.,Li, W.,Li, J.,Laage, S.,Siemer, A.B.,Wu, H.,McDermott, A.E. (登録日: 2017-03-21, 公開日: 2018-03-28, 最終更新日: 2024-05-01)

主引用文献

Mompean, M.,Li, W.,Li, J.,Laage, S.,Siemer, A.B.,Bozkurt, G.,Wu, H.,McDermott, A.E.
The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex.
Cell, 173:1244-1253.e10, 2018

PubMed Abstract: The RIPK1-RIPK3 necrosome is an amyloid signaling complex that initiates TNF-induced necroptosis, serving in human immune defense, cancer, and neurodegenerative diseases. RIPK1 and RIPK3 associate through their RIP homotypic interaction motifs with consensus sequences IQIG (RIPK1) and VQVG (RIPK3). Using solid-state nuclear magnetic resonance, we determined the high-resolution structure of the RIPK1-RIPK3 core. RIPK1 and RIPK3 alternately stack (RIPK1, RIPK3, RIPK1, RIPK3, etc.) to form heterotypic β sheets. Two such β sheets bind together along a compact hydrophobic interface featuring an unusual ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The crystal structure of a four-residue RIPK3 consensus sequence is consistent with the architecture determined by NMR. The RIPK1-RIPK3 core is the first detailed structure of a hetero-amyloid and provides a potential explanation for the specificity of hetero- over homo-amyloid formation and a structural basis for understanding the mechanisms of signal transduction.

PubMed: 29681455
DOI: 10.1016/j.cell.2018.03.032

実験手法

SOLID-STATE NMR