4XU6

Crystal structure of cross-linked MvINS R77C trimer at 1.9A resolution

Summary for 4XU6

• Entry DOI: 10.2210/pdb4xu6/pdb
• Related: 4XU4 4XU5 4XU7 4XU8 4XU9
• Descriptor: Uncharacterized protein, octyl beta-D-glucopyranoside, N-TRIDECANOIC ACID, ... (4 entities in total)
• Functional Keywords: unknown function
• Biological source: Mycobacterium vanbaalenii PYR-1
• Total number of polymer chains: 1
• Total formula weight: 22708.60

Authors

Ren, R.B.,Wu, J.P.,Yan, C.Y.,He, Y.,Yan, N. (deposition date: 2015-01-25, release date: 2015-10-14, Last modification date: 2024-03-20)

Primary citation

Ren, R.,Zhou, X.,He, Y.,Ke, M.,Wu, J.,Liu, X.,Yan, C.,Wu, Y.,Gong, X.,Lei, X.,Yan, S.F.,Radhakrishnan, A.,Yan, N.
PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels
Science, 349:187-191, 2015

PubMed Abstract: Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway.

PubMed: 26160948
DOI: 10.1126/science.aab1091

Experimental method

X-RAY DIFFRACTION (1.898 Å)