2021年1月14日 · The structure of the TM domains of human Scap and Insig-2 in the presence of 25HC reveals the interface between Insig and the SSD of Scap and explains the requirement of 25HC for complex formation, which involves the unwinding and bending of Scap-S4.

在ER膜上，氧化固醇可诱导Insig与HMGR相互作用，从而将泛素连接酶gp78募集至HMGR，导致HMGR泛素化并进入蛋白酶体降解。 当固醇不足时，SCAP不与Insig相互作用，SREBP-SCAP复合物就会进入含有COPII的囊泡中，被转运到高尔基体。

Scap (D428A), a well-documented mutant (Feramisco et al., 2005), and Scap (Q432A), a variant rationalized from our structural analysis (Yan et al., 2021), can both form complex with Insig in the absence of sterols, supporting the notion that maintenance of an unwound S4 and the nearby S2 segment is sufficient for Insig binding, even without a ...

当细胞内胆固醇含量较高时，内质网上的Insig蛋白能够通过跨膜区与Scap蛋白的甾醇感受结构域（Sterol sensing domain，SSD）相互作用，将SREBP2-Scap复合物锚定在内质网上，从而降低细胞内胆固醇的吸收和合成。

2021年4月23日 · 近日，颜宁和闫创业团队利用低温电子显微镜对25HC作用下Scap中的固醇敏感结构域（sterol sensing domain，SSD）和Insig-2中的跨膜（transmembrane，TM）部分进行解析，发现25HC分子夹在Scap的S4~S6段与Insig-2的TMs3/4段之间. Scap-S4中段的展开对与25HC和Insig结合至关重要[

2002年10月1日 · This paper describes insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi.

Scap and Insig, two proteins embedded in the membrane of the endoplasmic reticulum (ER), regulate the synthesis of cholesterol in animal cells by forming a dimer in the presence of high concentrations of cholesterol.

2021年6月29日 · Scap (D428A), a well-documented mutant (Feramisco et al., 2005), and Scap (Q432A), a variant rationalized from our structural analysis (Yan et al., 2021), can both form complex with Insig in the absence of sterols, supporting the notion that maintenance of an unwound S4 and the nearby S2 segment is sufficient for Insig binding, even without a ...

氧化甾醇能直接结合INSIG并促使它与SCAP-SREBP复合体结合。 INSIG-SCAP-SREBP蛋白复合体的形成也稳定了INSIG，避免其被泛素化降解。 除了INSIG外，其它调控SREBP2通路的因子还包括内质网脂筏蛋白ERLINs、泛素连接酶TRC8与RNF145、AKT、PAQR3以及HSP90等。

研究发现，炎症应激干扰了INSIG-SCAP-SREBPs通路负反馈调节，致使LDLr表达失调，细胞大量摄取外源性胆固醇。 本文从INSIG-SCAP-SREBPs通路概述、功能以及炎症干扰INSIG-SCAP-SREBPs转运体功能进行综述。 INSIG—SCAP—SREBPs通路与炎症