RNF13是之前未描述的iduronate 2-sulfatase的相互作用因子,它修改了其糖化和成熟的过程
Valérie C Cabana1,2,3, Antoine Y Bouchard1,2,3, Audrey M Sénécal1,2,3
1Department of Chemistry, Université du Québec à Montréal (UQAM), Canada.
The FEBS journal
|December 12, 2025
概括
研究人员发现,RNF13影响亨特综合征蛋白 (IDS) 的成熟和降解. 在 RNF13 中,
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 粘多糖症II型 (亨特综合征) 是一种致命的溶酶体储存障碍,由酸二硫酸酶 (IDS) 缺乏引起.
- 适当的IDS处理和溶酶体向对其酶活性至关重要,但细胞内动力学尚不清楚.
研究的目的:
- 调查E3无素酶RNF13在IDS的细胞内处理和贩运中的作用.
- 阐明控制IDS成熟和降解的机制.
主要方法:
- 预测AlphaFold 3结构,以确定潜在的蛋白质相互作用.
- 同免疫沉降试验证实了IDS-RNF13相互作用.
- 分析IDS糖化和溶酶体向的分析.
- 研究RNF13-RNF167异构体的形成及其对IDS处理的影响.
主要成果:
- RNF13与IDS的未成熟,低糖化形式相互作用,影响其成熟.
- RNF13与RNF167形成异构体,调节了这两种蛋白质的溶酶体贩运.
- RNF13的E3结合酶活性对于产生低糖化IDS形式至关重要,该形式由蛋白质酶体迅速降解.
- RNF13保护IDS免受蛋白质体的降解,表明其在成熟和降解中的双重作用.
结论:
- RNF13在IDS的成熟和降解途径中发挥着重要作用.
- 与单个酶相比,RNF13-RNF167异构体对IDS处理具有独特的影响.
- 了解RNF13的功能为亨特综合征的发病和潜在的治疗点提供了新的见解.
相关概念视频
Protein Modifications in the RER
6.8K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
6.8K
Nonsense-mediated mRNA Decay
11.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.6K
Protein Folding Quality Check in the RER
5.0K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
5.0K
Transcriptional Regulation: Riboswitches
520
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
520
Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
Regulation of Nuclear Protein Sorting
3.2K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.2K


