CAREER: Structural and Functional Elucidation of Strigolactone Signaling Pathway

该项目旨在利用结构生物学结合生物化学和植物生物学方法来阐明独脚金内酯（SL）的传感机制，独脚金内酯是一类新兴的和独特的植物激素，调节植物生长和发育的许多方面。虽然SL的研究历史较短，但在揭示其在控制植物生理和根际信号传导中的关键作用方面取得了快速进展。尽管有这些重大进展，关于激素感知、信号转导和激素代谢调节机制的几个关键问题仍然没有答案。该项目将支持综合研究，教育和推广计划，重点是通过利用先进的跨学科方法研究SL信号调节的结构-功能。该项目产生的知识可能对理解SL途径的生物学和推进农业技术产生深远影响，包括作物和寄生杂草的发芽控制。此外，作为研究活动的一个组成部分，该项目将创建一个独特的教学平台和外展计划，以鼓励年轻学生通过两个主要实施来追求STEM知识：（a）通过实施整合先进可视化工具的互动课程来开发现代生物化学课堂;（B）通过开创性的吸引人的讲习班来激励下一代科学家，促进对代表性不足的群体的STEM教育。最近对SL信号传导的关键成分的鉴定，包括水解酶受体，E3泛素（Ub）连接酶和AAA+ ATP酶伴侣蛋白样转录抑制蛋白家族，开辟了新的途径，研究进化，生物化学和生理学的这一途径及其对各种各样的发育过程的影响。然而，这类植物生长调节剂的信号转导途径的机械理解将仍然难以捉摸，直到SL信号复合物的结构和生化功能被阐明。因此，本项目的主要研究目标是：（1）从生物化学、结构和植物体内研究SL-信号复合物的功能状态。(2)揭示AAA+ ATP酶伴侣蛋白样转录抑制蛋白的作用模式，以及它们在SL生理反应调节中的作用。(3)利用结构生物学和植物生物学方法，阐明SL依赖性与泛素蛋白酶体系统，特别是与MAX2泛素连接酶和转录抑制因子相关的分子基础。这项研究的成果不仅可以弥补SL途径生物学理解的关键差距，而且还可能揭示植物信号传导和泛素蛋白酶体途径的新范式。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

This project is aimed at leveraging structural biology in combination with biochemistry and plant biology methods to elucidate the sensing mechanism of strigolactones (SLs), an emerging and unique class of plant hormones that regulate many aspects of plant growth and development. Although SL research has a short history, rapid progress has been made in unveiling its critical role in controlling plant physiology and rhizosphere signaling. Despite these significant advances, several key questions concerning the mechanisms of hormone perception, signal transduction, and regulation of hormone metabolism remain unanswered. This project will support an integrated research, education, and outreach program that focuses on the study of the structure-function of SL signaling regulation by utilizing advanced interdisciplinary approaches. The knowledge generated from this project may have far reaching impacts in understanding the biology of the SL pathway and advancing technologies in agriculture, including germination control of crops and parasitic weeds. Additionally, as an integral part of the research activities, this project will create a unique teaching platform and outreach program to encourage young students to pursue knowledge in STEM with two major implementations: (a) developing a modern biochemistry classroom by implementing an interactive curriculum that integrates advanced visualization tools; (b) promoting STEM education for underrepresented groups by pioneering engaging workshops to inspire the next generation of scientists.The recent identification of the key components of SL signaling, including a hydrolase receptor, an E3 ubiquitin (Ub) ligase, and a family of AAA+ ATPase chaperonin-like transcriptional repressor proteins, open up new avenues of investigation on the evolution, biochemistry, and physiology of this pathway and its impacts on a diverse array of developmental processes. However, a mechanistic understanding of the signal transduction pathway for this class of plant growth regulators will remain elusive until the structure and biochemical function of the SL signaling complex are elucidated. Therefore, the main research objectives of this project are to: (1) Study biochemically, structurally, and in planta the functional state of the SL-signaling complex. (2) Reveal the mode of action of AAA+ ATPase chaperonin-like transcriptional repressor proteins, and their role in regulation of SL physiological responses. (3) Elucidate the molecular basis of SL-dependent association with the ubiquitin proteasome system, in particularly with the MAX2 ubiquitin ligase, and the transcriptional repressors, by utilizing structural biology and plant biology approaches. Outcomes of this research may not only close a critical gap in understanding the biology of the SL pathway but may also uncover new paradigms in plant signaling and the ubiquitin proteasome pathway.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.