Defining the Effect of Mutations on Collagen Folding

定义突变对胶原蛋白折叠的影响

• 批准号: 7179297
• 负责人: MICHAEL A BRYAN
• 金额: $ 2.65万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7179297
• 关键词: Affect; Calorimetry; Circular Dichroism; Circular Dichroism Spectroscopy; Collagen; Collagen Type I; Condition; Connective Tissue; Data; Differential Scanning Calorimetry; Environment; Fiber; Glycine; Goals; Individual; Kinetics; Lead; Methods; Modeling; Mutation; Osteogenesis; Osteogenesis Imperfecta; Pathway interactions; Patients; Pattern; Peptides; Phenotype; Proteins; Range; Rate; Relative (related person); Research Design; Scanning; Severities; Site; Staging; Testing; Thermodynamics; bone; cost; insight; mineralization; mutant; triple helix

DESCRIPTION (provided by applicant): Type I collagen is an important protein in connective tissues such as bone. Collagen forms a trimer that is capable of self-association to form fibers. These fibers then become incorporated into bone during mineralization. Mutations in type I collagen lead to Osteogenesis Imperfecta (Ol) where there is defective bone formation. Mutations resulting in the substitution of one Gly residue within the repeating (Gly-Xaa- Yaa)n pattern of type I collagen triple helix are the major cause of Ol. Collagen folding in the presence of a mutation has been shown to be delayed. Our hypothesis is that this delay in folding is due to a pause at the mutation site leading to an intermediate state stable enough to have a significant impact on folding. Collagen model peptides will be used to study how type I collagen propagates through a glycine mutation in Ol using Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC). This study aims to determine whether the effects of different Gly mutations on collagen folding can ultimately provide insight into the varying phenotypes observed in Ol patients.

描述（由申请人提供）：I型胶原蛋白是结缔组织（例如骨骼）中的重要蛋白质。胶原蛋白形成一种能够自相关形成纤维的三聚体。然后，这些纤维在矿化过程中掺入骨骼中。 I型胶原蛋白中的突变导致骨形成缺陷的成骨不完美（OL）。在重复（Gly-XA-YAA）n型I型胶原蛋白三螺旋螺旋的模式中取代一个GLY残基的突变是OL的主要原因。 在存在突变的情况下，胶原蛋白折叠已显示为延迟。我们的假设是，这种折叠的延迟是由于突变部位停顿，导致中间状态稳定足以对折叠产生重大影响。胶原蛋白模型肽将用于研究I型胶原蛋白如何使用圆二色性（CD）和差扫描量热法（DSC）在OL中通过甘氨酸突变传播。这项研究旨在确定不同的糖突变对胶原蛋白折叠的影响是否可以最终洞悉OL患者中观察到的不同表型。