4L9U

Structure of C-terminal coiled coil of RasGRP1

4L9U の概要

• エントリーDOI: 10.2210/pdb4l9u/pdb
• 関連するPDBエントリー: 4L9M
• 分子名称: RAS guanyl-releasing protein 1, GLYCEROL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol: O95267
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13631.44

構造登録者

Iwig, J.S.,Vercoulen, Y.,Das, R.,Barros, T.,Limnander, A.,Che, Y.,Pelton, J.G.,Wemmer, D.E.,Roose, J.P.,Kuriyan, J. (登録日: 2013-06-18, 公開日: 2013-08-21, 最終更新日: 2024-02-28)

主引用文献

Iwig, J.S.,Vercoulen, Y.,Das, R.,Barros, T.,Limnander, A.,Che, Y.,Pelton, J.G.,Wemmer, D.E.,Roose, J.P.,Kuriyan, J.
Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1.
Elife, 2:e00813-e00813, 2013

PubMed Abstract: RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI:http://dx.doi.org/10.7554/eLife.00813.001.

PubMed: 23908768
DOI: 10.7554/eLife.00813

実験手法

X-RAY DIFFRACTION (1.6014 Å)