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Applications of transmembrane protein, endoplasmic reticulum liporaft proteins or antagonists or inhibitors of coding genes thereof

A technology that encodes genes and transmembrane proteins, and is applied in the field of transmembrane protein 6 family member 2 proteins to achieve the effect of reducing blood lipids and promoting the decline of levels

Pending Publication Date: 2021-09-03
SHENZHEN RES INST OF WUHAN UNIVERISTY
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Problems solved by technology

But the effect of ERLINs on lipid metabolism is still unknown

Method used

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  • Applications of transmembrane protein, endoplasmic reticulum liporaft proteins or antagonists or inhibitors of coding genes thereof
  • Applications of transmembrane protein, endoplasmic reticulum liporaft proteins or antagonists or inhibitors of coding genes thereof
  • Applications of transmembrane protein, endoplasmic reticulum liporaft proteins or antagonists or inhibitors of coding genes thereof

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Embodiment Construction

[0043] In order to facilitate those skilled in the art to understand and implement the present invention, the present invention will be described in further detail below in conjunction with the accompanying drawings. It should be understood that the implementation examples described here are only used to illustrate and explain the present invention, and are not intended to limit the present invention.

[0044] Such as figure 1 As shown, TM6SF2 interacting proteins were screened using multi-step affinity purification coupled with tandem mass spectrometry

[0045] A. The multi-step affinity purification coupled mass spectrometry method is shown in the figure;

[0046] B. Add part of the concentrate after multi-step affinity purification (TAP) of the experimental group and the control group to 4-20% gradient gel, and use Coomassie Brilliant Blue to stain the protein after running the gel. The combined TM6SF2-TAP protein band is shown in the figure shown;

[0047] C. Screen the ...

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Abstract

The invention discloses applications of transmembrane protein, endoplasmic reticulum liporaft proteins or antagonists or inhibitors of coding genes thereof. Interaction between endoplasmic reticulum lipid raft proteins 1 and 2 (ERLIN1 and ERLIN2) with TM6SF2 and apolipoprotein B (APOB) is found by applying a multi-step affinity purification method in combination with mass spectrometry. The ERLINs and the TM6SF2 stabilize each other, and meanwhile, the TM6SF2 combines with the APOB through the two endoplasmic reticulum lumen sections. Although the ERLINs do not directly combine with the APOB, the APOB can be indirectly stabilized by stabilizing the TM6SF2. The E167K mutation affects the stability of APOB by reducing the TM6SF2 protein level. Reduction of Tm6sf2 or ERLINs protein expression by using adenovirus-associated viruses in mice can reduce APOB protein level in the liver, thereby reducing lipid level in blood. The invention provides a novel target and strategy for treating dyslipidemia.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the use of transmembrane protein 6 family member 2 (TM6SF2) protein and endoplasmic reticulum lipid raft protein 1 and 2 (ERLIN1, ERLIN2). Background technique [0002] Relationship between TM6SF2 and lipids in blood [0003] TM6SF2 is a gene encoding a 351 amino acid multispanning protein located on chromosome 19. It was cloned as a paralogous gene of TM6SF1 in 2000 and was first reported by L. Carim-Todd (L. Carim-Todd, 2000). Until 2014, several research teams almost simultaneously discovered another single-base mutation that was significantly associated with non-alcoholic fatty liver disease in addition to the PNPLA3 gene through the genome-wide association study (GWAS) research method. The point rs58542926, this mutation site is located on the TM6SF2 gene, which leads to the E167K mutation of the multi-transmembrane protein TM6SF2, which causes a non-synonymous change from glu...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61P3/06A61P3/04A61P5/00A61K38/17
CPCA61K45/06A61P3/06A61P3/04A61P5/00A61K38/1709
Inventor 宋保亮李博韬孙铭李云峰
Owner SHENZHEN RES INST OF WUHAN UNIVERISTY
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