ジャーナル: Nat Commun / 年: 2018 タイトル: Structural basis of RIP2 activation and signaling. 著者: Qin Gong / Ziqi Long / Franklin L Zhong / Daniel Eng Thiam Teo / Yibo Jin / Zhan Yin / Zhao Zhi Boo / Yaming Zhang / Jiawen Zhang / Renliang Yang / Shashi Bhushan / Bruno Reversade / Zongli Li / Bin Wu / 要旨: Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting- ...Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing proteins 1/2 (NOD1 and NOD2). Dysregulation of this signaling pathway leads to defects in bacterial detection and in some cases autoimmune diseases. Here, we show that the Caspase-activation-and-recruitment-domain (CARD) of RIP2 (RIP2-CARD) forms oligomeric structures upon stimulation by either NOD1-CARD or NOD2-2CARD. We reconstitute this complex, termed the RIPosome in vitro and solve the cryo-EM filament structure of the active RIP2-CARD complex at 4.1 Å resolution. The structure suggests potential mechanisms by which CARD domains from NOD1 and NOD2 initiate the oligomerization process of RIP2-CARD. Together with structure guided mutagenesis experiments at the CARD-CARD interfaces, we demonstrate molecular mechanisms how RIP2 is activated and self-propagating such signal.
想定した対称性 - らせんパラメータ - Δz: 4.936 Å 想定した対称性 - らせんパラメータ - ΔΦ: -101.373 ° 想定した対称性 - らせんパラメータ - 軸対称性: C1 (非対称) 解像度のタイプ: BY AUTHOR / 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 2.0beta) 詳細: Model building was based on a cropped-out density segment. Pseudo-crystallographic refinement showed that the central segment of the map is good until 3.5-3.7 A. 使用した粒子像数: 142330
Segment selection
選択した数: 658160
初期モデル
モデルのタイプ: OTHER 詳細: A tubular cylinder with 80 A width was used as the starting model.
最終 角度割当
タイプ: NOT APPLICABLE / ソフトウェア - 名称: RELION (ver. 2.0beta)
FSC曲線 (解像度の算出)
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原子モデル構築 1
精密化
空間: RECIPROCAL / プロトコル: RIGID BODY FIT / 温度因子: 202.7 / 当てはまり具合の基準: Rfree value