FOLDING AND DYNAMICS OF A MOLTEN GLOBULE

熔球的折叠和动力学

• 批准号: 6471595
• 负责人: ZHENG-YU PENG
• 金额: $ 3.63万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471595
• 关键词: biophysics; chemical stability; circular dichroism; conformation; disulfide bond; intermolecular interaction; lactalbumin; nuclear magnetic resonance spectroscopy; protein folding; protein sequence; protein structure; site directed mutagenesis; structural biology; thermodynamics

DESCRIPTION: The long term objective of this proposal is to understand the mechanism of protein folding, the process by which a newly synthesized polypeptide adopts its biological conformation. A general protein folding intermediate is the molten globule, a species characterized by compactness, near-native levels of secondary structure, and the absence of rigid, specific side chain packing. One of the best studied molten globules is that of alpha-lactalbumin (alpha-LA), a small two-domain protein. The richness of existing knowledge, the ability to probe the backbone topology by disulfide bond formation, and the availability of recombinant variants that are molten globules under non-denaturing conditions make alpha-LA an ideal model system for understanding the function of this intermediate in protein folding. The helical domain of alpha-LA molten globule has a native-like tertiary fold, which serves as a scaffold for organization of the rest of the polypeptide chain and a starting point from which to search for the correct side chain packing. The specific aims of this study are: (1) To understand the molecular interactions and the information in the primary sequence that determine the native-like tertiary fold in the alpha-LA molten globule. (2) To characterize the side chain dynamics in the molten globule and understand how the dynamics change upon formation of the native protein. To achieve these goals: (1) Alanine scanning mutagenesis and pairwise alanine substitutions will be used to determine the contribution of each side chain and its interaction to the specificity for formation of the native-like tertiary fold. (2) NMR relaxation measurements on selectively isotope labeled proteins will be used to study the dynamics of individual residues in the molten globule and to understand the transition from the molten globule to the native state of alpha-LA. These studies will provide foundations for understanding the molecular basis of human diseases caused by protein misfolding or aggregation, as well as for rational design of proteins with specific medical applications.

描述：本提案的长期目标是了解

项目成果

A minimum folding unit in the ankyrin repeat protein p16(INK4).

• DOI: 10.1006/jmbi.2000.3803
• 发表时间: 2000-06
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Bin Zhang;Zheng‐yu Peng

A model of dynamic side-chain--side-chain interactions in the alpha-lactalbumin molten globule.

α-乳清蛋白熔球中动态侧链-侧链相互作用的模型。

• DOI: 10.1110/ps.34101
• 发表时间: 2001
• 期刊: Protein science : a publication of the Protein Society
• 作者: Bai,P;Song,J;Luo,L;Peng,ZY
• 通讯作者: Peng,ZY

Hierarchical unfolding of the alpha-lactalbumin molten globule: presence of a compact intermediate without a unique tertiary fold.

α-乳清蛋白熔球的分层展开：存在紧凑的中间体，没有独特的三级折叠。

• DOI: 10.1006/jmbi.2000.3660
• 发表时间: 2000
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Chakraborty,S;Peng,Z
• 通讯作者: Peng,Z

Contribution of individual residues to formation of the native-like tertiary topology in the alpha-lactalbumin molten globule.

单个残基对α-乳清蛋白熔球中类似天然三级拓扑结构的形成的贡献。

• DOI: 10.1006/jmbi.1998.1826
• 发表时间: 1998
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Song,J;Bai,P;Luo,L;Peng,ZY
• 通讯作者: Peng,ZY