6M49

cryo-EM structure of Scap/Insig complex in the present of 25-hydroxyl cholesterol.

Summary for 6M49

• Entry DOI: 10.2210/pdb6m49/pdb
• EMDB information: 30074
• Descriptor: Insulin-induced gene 2 protein, Sterol regulatory element-binding protein cleavage-activating protein,Sterol regulatory element-binding protein cleavage-activating protein, 25-HYDROXYCHOLESTEROL (3 entities in total)
• Functional Keywords: scap, insig, cholesterol, sterol sensing, 25-hydroxycholesterol, srebp, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 88447.72

Authors

Yan, R.,Cao, P.,Song, W.,Qian, H.,Du, X.,Coates, H.W.,Zhao, X.,Li, Y.,Gao, S.,Gong, X.,Liu, X.,Sui, J.,Lei, J.,Yang, H.,Brown, A.J.,Zhou, Q.,Yan, C.,Yan, N. (deposition date: 2020-03-06, release date: 2021-01-20, Last modification date: 2025-06-25)

Primary citation

Yan, R.,Cao, P.,Song, W.,Qian, H.,Du, X.,Coates, H.W.,Zhao, X.,Li, Y.,Gao, S.,Gong, X.,Liu, X.,Sui, J.,Lei, J.,Yang, H.,Brown, A.J.,Zhou, Q.,Yan, C.,Yan, N.
A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
Science, 371:-, 2021

PubMed Abstract: The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and -2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.

PubMed: 33446483
DOI: 10.1126/science.abb2224

Experimental method

ELECTRON MICROSCOPY (3.7 Å)