相关实验视频

Updated: May 23, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

揭示功能性热点:K-RAS的温度依赖晶体学突出显示了可吸收和可吸收的网站

Samuel L Deck^1,2, Megan Xu^1,2, Shawn K Milano^1,2

¹Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.

bioRxiv : the preprint server for biology

|March 10, 2025

概括

多温度X射线晶体学揭示了在冷温度下错过的关键K-RAS蛋白质动态. 这一突破通过发现隐藏的全位,为难以治疗的癌症确定了新的药物标.

科学领域:

结构生物学结构生物学
生物物理学的生物物理.
在瘤学瘤学.

背景情况:

K-RAS突变是许多癌症的关键驱动因素,但由于缺乏可用药物的标,开发有效的疗法一直是具有挑战性的.
标准的X射线结晶学通常使用冷温度,这可能会掩盖功能上重要的蛋白质动态.

研究的目的:

通过使用多温度X射线晶体学 (MT-XRC) 调查K-RAS的温度依赖性构造景观.
为了识别功能相关的K-RAS形状和在冷条件下隐藏的全位.

主要方法:

利用多温度X射线晶体学 (MT-XRC) 来捕捉K-RAS结构在各种温度范围内,从冷到生理.
分析了关键区域的形状变化,包括已知的全和药物结合口袋.

主要成果:

揭示了K-RAS的温度依赖的结构格局,突出了药物开发至关重要的动态状态.
鉴定了关键部位的显著构造变化,包括隐藏在冷温度下的全囊.
结构发现与大规模突变研究确定的区域保持一致,提供了功能性重要的全位的精确快照.

结论:

MT-XRC对于可视化标准冷式X射线晶体学遗漏的构造转换至关重要,使得"难以药物"蛋白质的向成为可能.
该研究为K-RAS信号提供了新的结构洞察力,并为合理的药物设计确定了新的治疗点.
该框架可用于发现针对其他具有挑战性的药物点的治疗机会.

更多相关视频

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

相关概念视频

The Ras Gene

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...

Small GTPases - Ras and Rho

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:

Receptor Tyrosine Kinases

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...