反平行(数学)
连接器
蛋白质丝
分子
中间灯丝
螺旋线圈
结晶学
化学
角蛋白
半胱氨酸
材料科学
物理
生物
生物化学
量子力学
操作系统
磁场
细胞骨架
古生物学
有机化学
酶
细胞
计算机科学
作者
Peter M. Steinert,Lyuben N. Marekov,R.D.B. Fraser,David Parry
标识
DOI:10.1006/jmbi.1993.1161
摘要
One of the major obstacles to solving the full three-dimensional structure of keratin intermediate filaments (KIF) is the determination of the exact mode(s) of alignment of nearest-neighbor molecules; this in turn requires precise information of the lengths of the non-α-helical linker segments within the coiled-coil α helical heterodimer molecule. In this study, we have induced lysine-lysine and cysteine-cysteine crosslinks between keratin intermediate filament molecules in small assembly-competent oligomers, isolated them and then characterized the natures and locations of the crosslinks. Of more than 100 found, 21 quantitatively major crosslinks were used to obtain the relative axial alignments of rod domain segments by least-squares fitting methods. Three dominant modes of alignment were found. In each case the molecules are antiparallel with the first involving molecules in approximate register (stagger = -0·2 nm), the second involving molecules staggered so as to bring the 1B segments into approximate alignment (stagger = -16·1 nm), and the third involving molecules staggered so as to bring the 2B segments into approximate alignment (stagger= 28·2 nm). In addition, the data enable quantitative estimates to be made for the first time of the lengths of the non-coiled-coil segments (L1=2·5 nm, L12=1·6nm, L2=0·8 nm), and the total length of the rod domain (46·0 nm). Alignment of molecules according to these parameters permits construction of a two-dimensional surface lattice which displays a 1·6 nm (10 or 11 residue) overlap between similarly directed molecules, Together, the data predict six important overlapping sequence regions that recur about 16 times per 46 nm of filament length. Interestingly, synthetic peptides corresponding to these sequences, singly or in combination, significantly interfere with keratin filament structural integrity. These results thus represent the most significant set of structural constraints for KIF yet available and provide insights into how disease-causing mutations disrupt filaments and their organization in cells.
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