Folding Determinants of beta-Hairpin Peptides

β-发夹肽的折叠决定因素

• 批准号: 6930647
• 负责人: MARCEY L WATERS
• 金额: $ 21.51万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930647
• 关键词: chemical stability; high performance liquid chromatography; ionic bond; matrix assisted laser desorption ionization; peptide chemical synthesis; peptides; protein biosynthesis; protein folding; protein purification; protein structure function; structural biology; ubiquitin

DESCRIPTION (provided by applicant): With rapid advances in genomics, the next major undertaking is to determine the structure and function of the proteins encoded by newly discovered genes. However, current predictive ability for protein structure is limited, in part because the factors that define a single low energy fold are not yet well understood. Protein de novo design has demonstrated that simple binary coding of hydrophobic and hydrophilic residues is too simplistic a model to define a native-like structure. To gain insight into the factors that contribute to specificity in protein folding, we are investigating the ability of interactions of polarized C-H groups with aromatic rings to provide specificity to protein structure through weakly polar "hydrophobic" interactions. In proteins, this type of interaction includes, for example, edge-face interactions between two aromatic sidechains, the interaction of a lysine sidechain with an aromatic group, and the interaction of the axial hydrogens of carbohydrates with the x-cloud of an aromatic ring in carbohydrate binding proteins. We expect that these C-H...( interactions would provide stability and specificity to protein structure because the interaction consists of an electrostatic interaction between the electron-poor C-H and the x-cloud of the aromatic ring, in addition to hydrophobic and van der Waals components. We will investigate the nature of these interactions in model B-hairpin peptides and determine their impact on specificity of strand register in B-hairpins. Subsequently, we will determine their effect on folding of the protein ubiquitin, which has been shown to fold via the nucleation of a B-hairpin.

描述(申请人提供)：随着基因组学的快速发展，下一个主要任务是确定由新发现的基因编码的蛋白质的结构和功能。然而，目前对蛋白质结构的预测能力有限，部分原因是定义单个低能折叠的因素还没有被很好地理解。蛋白质从头设计已经证明，简单的疏水和亲水残基的二进制编码对于定义天然结构来说过于简单。为了深入了解导致蛋白质折叠特异性的因素，我们正在研究极化的C-H基团与芳香环的相互作用通过弱极性的“疏水”相互作用为蛋白质结构提供特异性的能力。在蛋白质中，这种类型的相互作用包括，例如，两个芳香族侧链之间的边-面相互作用，赖氨酸侧链与芳香基的相互作用，以及碳水化合物的轴向氢与碳水化合物结合蛋白中芳环的x-云的相互作用。我们预计这些C-H...(相互作用将为蛋白质结构提供稳定性和特异性，因为除了疏水和范德华成分外，这种相互作用还包括低电子的C-H和芳环的x-云之间的静电相互作用。我们将研究模型B-发夹多肽中这些相互作用的性质，并确定它们对B-发夹中链注册的特异性的影响。随后，我们将确定它们对蛋白质泛素折叠的影响，泛素已被证明通过B-发夹的成核而折叠。