用于将WASH亚单元FAM21与内体SNX27-Retromer复合体结合的结构基础
Qian Guo1, Kai-En Chen1, Manuel Gimenez-Andres2
1The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia.
概括
复原体-SNX27复合体通过FAM21连接到WASH复合体,调节内体循环的活性核. 这种相互作用对于形成功能性内体细胞膜领域至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 内体膜贩运依赖于蛋白质外套和富含活性蛋白的域名.
- 像SNX27一样,复原体复合体和排序nexin (SNXs) 是关键参与者.
- SNX27-Retromer与威斯科特-阿尔德里希综合征蛋白和SCAR同类 (WASH) 复合体相互作用,以组织actin.
研究的目的:
- 阐明SNX27-Retromer与WASH复合体之间的相互作用的分子机制.
- 了解FAM21如何调解这些相互作用.
- 确定这些相互作用对内体循环的功能意义.
主要方法:
- 在X射线晶体学.
- 计算建模计算建模
- 生物化学测定 生物化学测定
- 细胞验证研究的研究.
主要成果:
- FAM21通过酸性-Asp-Leu-Phe (aDLF) 基因与SNX27结合,通过重叠重复和Pro-Leu基因与Retromer结合.
- 这些相互作用涉及Retromer的VPS35和VPS29子单元.
- 突变主要的VPS35结合部位部分破坏了WASH关联,但没有破坏货物回收,这表明功能冗余.
结论:
- 建立了SNX27-Retromer与WASH复合物合的详细分子基础.
- 叠加和多重相互作用对于WASH复杂的招募和内体活动至关重要.
- 这些发现对于理解内体细胞膜回收领域的动态组合至关重要.
相关概念视频
SNAREs and Membrane Fusion
10.8K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.8K
Rab Cascades
2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
Fusion of Secretory Vesicles with the Plasma Membrane
11.0K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.0K
Protein Translocation Machinery on the ER Membrane
4.6K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.6K
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K


