在Stu2/XMAP215-家族微管聚合酶的生化机制
Binnu Gangadharan1, Daniel L Kober2, Luke M Rice1,2
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
这项研究揭示了Stu2/XMAP215聚合酶对微管体生长调节的定量生物化学机制,表明它们像酶一样起作用. 这一发现提供了关于细胞骨动态和融合进化的见解.
科学领域:
- 细胞骨的动力学
- 生物化学 生物化学
- 分子和细胞生物学分子和细胞生物学
背景情况:
- 微管动力学对细胞过程至关重要,但其调节尚未完全理解.
- 使用管结合TOG域的Stu2/XMAP215家族聚合酶是微管生长的关键调节者.
- TOG域与聚合酶活性之间的确切关系尚不清楚.
研究的目的:
- 量化定义Stu2/XMAP215微管聚合酶活性的生物化学机制.
- 为了测试一种类似酶的模型对Stu2的适用性,类似于actin聚合酶.
- 为了将Stu2活动与其TOG域数量和蛋白结合动力学相关联.
主要方法:
- 酶动力学测试用于测量微管体生长率.
- 对TOG域的生物化学测量:素结合亲和力和解离率.
- 应用定量生物化学模型来分析Stu2活动.
主要成果:
- 斯图2表现出类似酶的动力学,微管的生长速度显示出对氨酸度的过度依赖.
- 微管末端的Stu2度保持不变,无论管度如何.
- 观察到高亲和度 (10nM) 和缓慢解离 (0.03s-1) 的TOG:tubulin相互作用.
结论:
- 斯图2作为一个高效的管穿天线,其活动主要受管:TOG协会率的限制.
- 已经确定了基于TOG的微管聚合酶的定量生物化学机制.
- 无关的微管和动因聚合酶之间共享的类似酶的机制说明了细胞骨中的融合进化.
相关概念视频
Microtubule Associated Proteins (MAPs)
4.5K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.5K
Destabilization of Microtubules
2.8K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.8K
Microtubule Instability
5.3K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.3K
Restarting Stalled Replication Forks
5.9K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.9K
Drugs that Stabilize Microtubules
2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Translesion DNA Polymerases
10.2K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.2K


