3BS5

Crystal Structure of hCNK2-SAM/dHYP-SAM Complex

3BS5 の概要

• エントリーDOI: 10.2210/pdb3bs5/pdb
• 関連するPDBエントリー: 3BS7
• 分子名称: Protein aveugle, Connector enhancer of kinase suppressor of ras 2 (3 entities in total)
• 機能のキーワード: sterile alpha motif, sam domain, sam domain dimer, sam domain complex, cytoplasm, membrane, sensory transduction, vision, alternative splicing, coiled coil, phosphoprotein, polymorphism, signaling protein-membrane protein complex, signaling protein/membrane protein
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• 細胞内の位置: Cytoplasm: Q8ML92 Q8WXI2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22324.39

構造登録者

Rajakulendran, T.,Ceccarelli, D.F.,Kurinov, I.,Sicheri, F. (登録日: 2007-12-22, 公開日: 2008-02-26, 最終更新日: 2024-11-06)

主引用文献

Rajakulendran, T.,Sahmi, M.,Kurinov, I.,Tyers, M.,Therrien, M.,Sicheri, F.
CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
Proc.Natl.Acad.Sci.USA, 105:2836-2841, 2008

PubMed Abstract: RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.

PubMed: 18287031
DOI: 10.1073/pnas.0709705105

実験手法

X-RAY DIFFRACTION (2 Å)