FACTORS AFFECTING THE SECONDARY STRUCTURE IN PROTEINS

影响蛋白质二级结构的因素

• 批准号: 2173743
• 负责人: W C JOHNSON
• 金额: $ 15.18万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2173743
• 关键词: chemical aggregate; circular dichroism; conformation; nuclear magnetic resonance spectroscopy; peptide chemical synthesis; protein engineering; protein folding; protein purification; protein sequence; protein structure; solvents

It is generally accepted that the amino acid sequence of a protein determines its ultimate three-dimensional structure. In the hierarchic view, the primary structure determines regular repeating secondary structures, which in turn fold up into a tertiary structure. Researchers have noted the certain amino acids have a preference for a given secondary structure, and a number of schemes have been developed that use amino acid preferences to predict secondary structure from primary structure. If the amino acid preferences were absolute, then the protein folding problem would undoubtedly be solved. Since the preferences are not absolute, one can view the protein folding problem in reverse and ask the question: Why is each amino acid found in every type of secondary structure? If this question can be answered, we might be well on our way to solving the protein folding problem, and our first two specific aims deal with this question. 1. We propose to investigate exceptional sequences of amino acids that are predicted to be in one secondary structure from amino acid preferences, that are found in another secondary structure. These are the interesting sequences because they are the demonstrated failures of our prediction methods. Our working hypothesis is that the environment is important in determining the secondary structure formed by an amino acid sequence. We would synthesize exceptional sequences and follow the secondary structure as a function of solvent system. 2. We propose to investigate the hypothesis that a few amino acids nucleate the formation of a secondary structure, and that continuation of the structure is relatively independent of the amino acids until continuation of the structure is broken. Sequences that readily form an alpha-helix or beta-strand in solution are well known; can we induce indifferent amino acids to continue this structure? 3. We propose to use circular dichroism to investigate the secondary structure of proteins of current interest, and to improve our system of analyzing CD for secondary structure. This continues our longstanding interest in relating the spectra of proteins to their secondary structure, but with considerably reduced emphasis.

一般认为蛋白质的氨基酸序列 决定了它最终的三维结构。 在分层 视图中，主结构确定定期重复的次结构 结构，其又折叠成三级结构。 研究人员 已经注意到某些氨基酸对给定的二级结构具有偏好， 结构，已经开发了许多使用氨基酸 从一级结构预测二级结构的偏好。 如果 氨基酸的偏好是绝对的，那么蛋白质折叠的问题 无疑会被解决。 由于偏好不是绝对的， 我可以反过来看待蛋白质折叠问题，并问这样一个问题：为什么 每种氨基酸都存在于每种二级结构中吗？ 如果这 如果这个问题能够得到回答，我们可能会很好地解决这个问题。 蛋白质折叠的问题，我们的前两个具体目标处理这个问题， 问题 1.我们建议研究特殊的氨基酸序列， 根据氨基酸偏好预测为一种二级结构， 存在于另一个二级结构中。 这些是有趣的 因为它们是我们预测的失败 方法. 我们的工作假设是，环境是重要的， 确定由氨基酸序列形成的二级结构。 我们 会合成特殊序列并遵循二级结构 作为溶剂系统的函数。 2.我们建议研究少数氨基酸成核的假说 二级结构的形成以及二级结构的延续 结构是相对独立的氨基酸，直到继续 的结构被打破。 容易形成α-螺旋或 β-链在溶液中是众所周知的;我们能诱导无关的氨基吗？ 酸来延续这种结构？ 3.我们建议使用圆二色性来研究二次 目前感兴趣的蛋白质的结构，并改善我们的系统， 分析CD的二级结构。 这延续了我们长期以来 将蛋白质的光谱与其二级结构联系起来的兴趣， 但重点明显减少。