Structural basis of the specific protein-protein interactions underlying IF assem

IF 组装背后的特定蛋白质-蛋白质相互作用的结构基础

• 批准号: 8142487
• 负责人: PETER BURKHARD
• 金额: $ 25.46万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8142487
• 关键词: Architecture; C-terminal; Cells; Computer Simulation; Cytoskeletal Proteins; Electron Microscopy; Filament; Goals; Head; In Vitro; Intermediate Filament Proteins; Intermediate Filaments; Knowledge; Length; Mechanics; Methods; Modeling; Molecular; Molecular Weight; Pathway interactions; Periodicity; Phosphorylation; Positioning Attribute; Property; Proteins; Regulation; Resolution; Roentgen Rays; Role; Shapes; Site; Spectrum Analysis; Structure; Tail; Vimentin; X-Ray Crystallography; analytical ultracentrifugation; base; dimer; meetings; polypeptide; protein protein interaction; retinal rods; wound

As indicated in the overview section of this PPG, vimentin consists of a central rod domain flanked by nona-helical head and tail domains. The central rod domain reveals a pronounced seven-residue periodicity, (abcdefg)n, in the distribution of apolar residues. Within this repeat, positions a and d are preferentially occupied by small apolar residues like Leu, lie. Met or Val, typical for a so-called coiled-coil structure (1). A coiled coil is formed by two or more a-helices wound around each other in a 'superhelix', and is a widespread structural motif in proteins (2, 3). This common structural motif enables IF proteins to self-assemble into 10-nm filaments in vitro In the absence of any auxiliary proteins or factors. These filaments are rope-like assemblies made from two to six 4.5-nm protofibrils (i.e., containing eight IF polypeptides each) which, in turn, are made of two intertwined 3-nm protofilaments each (4, 5). Although the molecular architecture of the 3-nm protofilament has not yet been precisely defined, it appears to be made from two antiparallel IF dimers, the latter being 2-stranded a-helical coiled-coils (i.e., formed via the central rod domain) of two parallel, in-register IF polypeptides (also see Figure 6).

如本PPG的概述部分所示，波形蛋白由两侧为九螺旋头部和尾部结构域的中心杆结构域组成。中心杆域揭示了一个显着的七个残基的周期性，（abcdefg）n，在非极性残基的分布。在该重复序列中，位置a和d优先被小的非极性残基如Leu、lie占据。Met或瓦尔，通常用于所谓的卷曲螺旋结构（1）。卷曲螺旋由两个或更多个α-螺旋以“超螺旋”相互缠绕形成，并且是蛋白质中广泛存在的结构基序（2，3）。这种共同的结构基序使IF蛋白能够在体外自组装成10 nm的细丝，而不需要任何辅助蛋白或因子。这些细丝是绳状的集合体 由2到6个4.5-nm的原纤维制成（即，每个含有8个IF多肽），其依次由两个相互缠绕的3-nm原丝组成（4，5）。虽然3-nm原丝的分子结构尚未精确定义，但它似乎是由两个反平行的IF二聚体制成的，后者是2-链α-螺旋卷曲螺旋（即，通过中心杆结构域形成）的两个平行的、对齐的IF多肽（也参见图6）。