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PDBsum entry 4xu4
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Unknown function
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PDB id
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4xu4
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References listed in PDB file
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Key reference
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Title
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Protein structure. Crystal structure of a mycobacterial insig homolog provides insight into how these sensors monitor sterol levels.
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Authors
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R.Ren,
X.Zhou,
Y.He,
M.Ke,
J.Wu,
X.Liu,
C.Yan,
Y.Wu,
X.Gong,
X.Lei,
S.F.Yan,
A.Radhakrishnan,
N.Yan.
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Ref.
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Science, 2015,
349,
187-191.
[DOI no: ]
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PubMed id
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Abstract
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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.
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