6ULG

Cryo-EM structure of the FLCN-FNIP2-Rag-Ragulator complex

6ULG の概要

• エントリーDOI: 10.2210/pdb6ulg/pdb
• EMDBエントリー: 20814
• 分子名称: Folliculin, GUANOSINE-5'-DIPHOSPHATE, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: flcn-fnip2, rag gtpases, ragulator, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 333995.13

構造登録者

Shen, K.,Rogala, K.B.,Yu, Z.H.,Sabatini, D.M. (登録日: 2019-10-08, 公開日: 2019-11-20, 最終更新日: 2025-05-21)

主引用文献

Shen, K.,Rogala, K.B.,Chou, H.T.,Huang, R.K.,Yu, Z.,Sabatini, D.M.
Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex.
Cell, 179:1319-1329.e8, 2019

PubMed Abstract: mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.

PubMed: 31704029
DOI: 10.1016/j.cell.2019.10.036

実験手法

ELECTRON MICROSCOPY (3.31 Å)