CAA: Mapping the Topology of Neuronal Nitric Oxide Synthase Bound to Calmodulin

CAA：绘制与钙调蛋白结合的神经元一氧化氮合酶的拓扑结构

• 批准号: 0718873
• 负责人: Regina Stevens-Truss
• 金额: $ 14.19万
• 依托单位: Kalamazoo College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0718873&HistoricalAwards=false
• 关键词: CAA; Mapping; Topology; Neuronal; Nitric

ABSTRACTNitric oxide synthase is an enzyme involved in a number of biological functions such as neuronal cell signaling and vascular tone. This enzyme exists as three distinct forms that are regulated differently in the body. One regulatory factor is the enzyme''s interaction with another protein called calmodulin. Calmodulin (CaM) is in fact involved in regulating over 40 different enzymes in cells, an action not completely understood. The project outlined here will make use of traditional protein footprinting methodologies coupled with mass spectrometry to unravel the mechanisms underlying CaM''s binding to and regulating the neuronal form of nitric oxide synthase (nNOS). More specifically, this research will give insights into the folded structure of the proteins as they relate to the functioning of neuronal cells. The broader impacts of this research are that it will provide much needed information regarding the role of CaM in regulating cellular functions, and in particular will shed light on the regulation of nNOS. This research will additionally provide undergraduate students at Kalamazoo College the opportunity to conduct research at the cutting-edge of genomics and proteomics. By conducting mass spectrometric studies coupled with bioinformatics techniques, graduates will be better prepared to advance in this new era of biochemistry research. This research will add to the commitment to the biochemistry and molecular biology programs at the College already made by the Howard Hughes Medical Institute to support bioinformatics modules incorporated into teaching curriculum. Funding for this research will additionally help the PI, a member of an underrepresented minority, attract and retain underrepresented students in biochemical research, and will provide these students a challenging and exciting problem to study. Kalamazoo College has been recently awarded an NSF S-STEM grant to be used to provide scholarships to newly recruited underrepresented students to the College who plan to pursue science and math as a course of study. The PI intends to use funds awarded to provide summer stipends for the S-STEM scholars to engage them in research projects as early as during the summer of their first year.

摘要一氧化氮合成酶是一种参与神经细胞信号转导和血管紧张性等多种生物学功能的酶。这种酶以三种不同的形式存在，在体内受到不同的调节。其中一个调节因素是S与另一种名为钙调蛋白的蛋白质相互作用的酶。钙调素(CaM)实际上参与了细胞中40多种不同的酶的调节，这一作用尚不完全清楚。本文概述的项目将利用传统的蛋白质足迹方法结合质谱学来揭示钙调素S与一氧化氮合酶(NNOS)神经元形式结合和调控的机制。更具体地说，这项研究将深入了解蛋白质的折叠结构，因为它们与神经细胞的功能有关。这项研究的更广泛的影响是，它将提供关于CaM在调节细胞功能中的作用的迫切需要的信息，特别是将有助于阐明nNOS的调节。这项研究还将为卡拉马祖学院的本科生提供进行基因组学和蛋白质组学前沿研究的机会。通过结合生物信息学技术进行质谱学研究，毕业生将更好地为在这个生物化学研究的新时代取得进步做好准备。这项研究将增加霍华德·休斯医学院已经做出的对生物化学和分子生物学项目的承诺，以支持将生物信息学模块纳入教学课程。这项研究的资金还将帮助代表不足的少数派吸引和留住生化研究中代表不足的学生，并将为这些学生提供一个具有挑战性和激动人心的学习问题。卡拉马祖学院最近获得了国家科学基金会S-STEM助学金，用于为学院新录取的未被充分代表的学生提供奖学金，这些学生计划攻读科学和数学作为一门课程。国际和平基金会打算利用发放的资金，为S-STEM学者提供暑期津贴，让他们最早在第一年的夏天就参与研究项目。