7MFE

Autoinhibited BRAF:(14-3-3)2 complex with the BRAF RBD resolved

7MFE の概要

• エントリーDOI: 10.2210/pdb7mfe/pdb
• EMDBエントリー: 23814
• 分子名称: Serine/threonine-protein kinase B-raf, 14-3-3 protein zeta/delta, ZINC ION (3 entities in total)
• 機能のキーワード: b-raf, 14-3-3, b-raf complex, b-raf monomer, inactive b-raf, serine/threonine-protein kinase b-raf, rbd, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140382.70

構造登録者

Martinez Fiesco, J.A.,Ping, Z.,Durrant, D.E.,Morrison, D.K. (登録日: 2021-04-09, 公開日: 2022-01-26, 最終更新日: 2024-11-13)

主引用文献

Martinez Fiesco, J.A.,Durrant, D.E.,Morrison, D.K.,Zhang, P.
Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding.
Nat Commun, 13:486-486, 2022

PubMed Abstract: RAF kinases are essential effectors of RAS, but how RAS binding initiates the conformational changes needed for autoinhibited RAF monomers to form active dimers has remained unclear. Here, we present cryo-electron microscopy structures of full-length BRAF complexes derived from mammalian cells: autoinhibited, monomeric BRAF:14-3-3:MEK and BRAF:14-3-3 complexes, and an inhibitor-bound, dimeric BRAF:14-3-3 complex, at 3.7, 4.1, and 3.9 Å resolution, respectively. In both autoinhibited, monomeric structures, the RAS binding domain (RBD) of BRAF is resolved, revealing that the RBD forms an extensive contact interface with the 14-3-3 protomer bound to the BRAF C-terminal site and that key basic residues required for RBD-RAS binding are exposed. Moreover, through structure-guided mutational studies, our findings indicate that RAS-RAF binding is a dynamic process and that RBD residues at the center of the RBD:14-3-3 interface have a dual function, first contributing to RAF autoinhibition and then to the full spectrum of RAS-RBD interactions.

PubMed: 35078985
DOI: 10.1038/s41467-022-28084-3

実験手法

ELECTRON MICROSCOPY (4.07 Å)