8UWC

Site-one protease without SPRING

8UWC の概要

• エントリーDOI: 10.2210/pdb8uwc/pdb
• EMDBエントリー: 42661
• 分子名称: Membrane-bound transcription factor site-1 protease, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: serine protease cholesterol metabolism zymogen activation protein complex glycoprotein secretory pathway, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 114105.00

構造登録者

Kober, D.L. (登録日: 2023-11-06, 公開日: 2024-07-10, 最終更新日: 2024-11-06)

主引用文献

Hendrix, S.,Dartigue, V.,Hall, H.,Bawaria, S.,Kingma, J.,Bajaj, B.,Zelcer, N.,Kober, D.L.
SPRING licenses S1P-mediated cleavage of SREBP2 by displacing an inhibitory pro-domain.
Nat Commun, 15:5732-5732, 2024

PubMed Abstract: Site-one protease (S1P) conducts the first of two cleavage events in the Golgi to activate Sterol regulatory element binding proteins (SREBPs) and upregulate lipogenic transcription. S1P is also required for a wide array of additional signaling pathways. A zymogen serine protease, S1P matures through autoproteolysis of two pro-domains, with one cleavage event in the endoplasmic reticulum (ER) and the other in the Golgi. We recently identified the SREBP regulating gene, (SPRING), which enhances S1P maturation and is necessary for SREBP signaling. Here, we report the cryo-EM structures of S1P and S1P-SPRING at sub-2.5 Å resolution. SPRING activates S1P by dislodging its inhibitory pro-domain and stabilizing intra-domain contacts. Functionally, SPRING licenses S1P to cleave its cognate substrate, SREBP2. Our findings reveal an activation mechanism for S1P and provide insights into how spatial control of S1P activity underpins cholesterol homeostasis.

PubMed: 38977690
DOI: 10.1038/s41467-024-50068-8

実験手法

ELECTRON MICROSCOPY (2.27 Å)