双层中的H-ras蛋白:相互作用和结构扰乱
Alemayehu A Gorfe1, Arneh Babakhani, J Andrew McCammon
1Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, and Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365, USA.
Journal of the American Chemical Society
|September 21, 2007
概括
拉斯GTPases通过脂质修饰在细胞膜上. 这项研究详细介绍了H-ras与脂质双层的相互作用,揭示了性质如何影响膜组织和纳米集群形成.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 拉斯GTPases需要膜 anchoring 的功能.
- 它们在细胞分裂,发育和癌症中的作用很重要.
- 膜插入和复杂结构的精确机制仍然不清楚.
研究的目的:
- 为了研究H-ras膜和DMPC双层之间的原子相互作用.
- 为了阐明H-ras膜协会的结构基础.
- 了解H-ras如何为膜纳米集群组织做出贡献.
主要方法:
- 在DMPC双层中对全长H-ras蛋白结构的计算表征.
- 详细分析了蛋白质-脂质界面上的原子相互作用.
主要成果:
- 棕化半氨酸和Met182通过结和范德瓦尔斯相互作用促进了膜亲和力.
- 的极侧链稳定了它在双层中的方向.
- 观察到局部双层扰动,取决于插入深度和局部,由催化域和链接器调节.
结论:
- 特定的键和杆灵活性决定了ras-DMPC的相互作用模式.
- 提供了Ras GTPase参与膜纳米集群组织的结构证据.
- 进步了解Ras GTPase膜动力学和功能.
相关概念视频
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Rab Cascades
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.
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...

