对人类ABCD3介导的过氧体乙烯-CoA转位的结构洞察力
Yang Li1,2, Zhi-Peng Chen1, Da Xu1,2
1Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, and Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Cell discovery
|September 2, 2024
概括
人类的ABCD3载体促进过氧体中的脂肪酸分解. 化EM结构揭示了ABCD3如何与基质和ATP结合,为脂肪酸氧化和相关肝脏疾病提供了洞察力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 人类ATP结合盒 (ABC) 载体ABCD1-3是脂肪基-CoAβ-氧化过程中至关重要的过氧体膜蛋白.
- ABCD3 特别携带分支链脂肪酸,其功能障碍导致严重的肝脏疾病,如肝炎.
研究的目的:
- 阐明人类ABCD3在脂肪酸运输中的分子机制.
- 为了确定ABCD3基质特异性和ATP依赖传输的结构基础.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于获得ABCD3.3的高分辨率结构.
- 生物化学试验,包括基质刺激的ATPase活性试验.
主要成果:
- 在2.9 Å和3.2 Å分辨率下,确定了ABCD3与phytanoyl-CoA和ATP结合的两个冷EM结构.
- 在ABCD3中,植物甲基-CoA结合点与ABCD1不同,每个分子与单个跨膜域结合.
- ATP结合会诱导ABCD3的矩阵开放形态,转位腔内有CoA分子,这表明不同的运输状态.
结论:
- 确定的结构为ABCD3.3的运输周期提供了前所未有的洞察力.
- 这些发现促进了对脂肪酸氧化途径和ABCD3相关肝病的分子病理学的理解.
相关概念视频
Protein Import into the Peroxisomes
3.4K
Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
3.4K
ABC Transporters: Importer
2.7K
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
2.7K
ABC Transporters: Exporter
4.2K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
4.2K
Translocation of Proteins into the Mitochondria
3.1K
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,...
3.1K
Peroxisomes
11.4K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
11.4K
Pyruvate Oxidation
158.6K
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
158.6K


