由膜内金属蛋白酶SpoIVFBB的基质参与
Melanie A Orlando1, Hunter J T Pouillon1, Saikat Mandal1
1Dept. of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Nature communications
|October 17, 2024
概括
这项研究揭示了S2P膜内金属蛋白酶,如SpoIVFB,如何在细胞膜内捕获和处理基质. 这些发现阐明了在脂质环境中化水解的机制.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子微生物学 分子微生物学
背景情况:
- 在生命的各个领域,S2P 内膜金属蛋白酶对于各种信号通路至关重要.
- 在脂质膜内S2P蛋白酶的基质结和水解的精确机制仍然不太清楚.
研究的目的:
- 确定由S2P金属蛋白酶SpoIVFB的基质识别和催化结构的基础.
- 阐明S2P蛋白酶如何在疏水膜环境中将基质定位为水解.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与其基质Pro-σK结合的SpoIVFB的结构.
- 生物化学测试以验证结构发现.
- 模拟分子动力学以调查水的获取和脂质相互作用.
主要成果:
- 冷-EM结构透露了SpoIVFB的位置Pro-σK通过β-sheet增强机制.
- 确定了Pro-σK和SpoIVFB的域间链接器之间的关键相互作用.
- 提出了通往活性部位的可信的水接入途径,以及膜脂质在基质捕获中的潜在作用.
结论:
- 这项工作为S2P内膜金属蛋白酶的机制提供了关键的见解.
- 这些发现解释了这些酶如何在脂质膜内捕获和定向基质进行水解.
- 这项研究有助于我们对膜内蛋白解和膜蛋白功能的理解.
相关概念视频
Membrane Asymmetry Regulating Transporters
4.3K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.3K
Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Porin Insertion in the Outer Mitochondrial Membrane
2.8K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
2.8K
Structure of Porins
2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
2.9K
Protein Transport into the Inner Mitochondrial Membrane
3.6K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.6K
Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K


