Sequence dependence of kinetics and morphology of collagen model peptide self-assembly into higher order structures
Sequence dependence of kinetics and morphology of collagen model peptide self-assembly into higher order structures
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DOI：
10.1110/ps.083441308
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发表时间：
2008-06-01
期刊：
影响因子：
8
通讯作者：
Brodsky, Barbara
中科院分区：
文献类型：
--
作者：
Kar, Karunakar;Wang, Yuh-Hwa;Brodsky, Barbara
三螺旋多肽(Pro-Hyp-Gly)(10)自组装成高阶结构的过程在许多特征上类似于胶原纤维形成的成核-生长机制，但自组装肽的不规则形态与体内胶原形成的有序纤维和网络结构形成了鲜明的对比。(Pro-Hyp-Gly)(10)肽中心区域的氨基酸序列是不同的，并发现影响自组装的动力学和形成的高阶结构的性质。中心三联体的单一氨基酸变化产生了类似于(Pro-Hyp-Gly)(10)的不规则的高阶结构，但一个Pro到Ala或Leu的单一变化明显延缓了自结合的速度。从IV型胶原引入富含Hyp的疏水序列导致延伸纤维的更规则的超结构，有时表现出类似于基底膜网络中的IV型胶原的超卷曲和分支特征。一些肽的中心Pro-Hyp序列被带电残基或III型胶原的九个残基疏水区域取代，在标准条件下失去了自结合的能力。不能自组装的原因可能是亚氨基酸的损失，以及疏水/静电残基缺乏适当的分布。替代单一甘氨酸残基的效果也被检验，作为胶原疾病的模型，如成骨不全和Alport综合征。出乎意料的是，Gly到Ala的取代干扰了(Pro-Hyp-Gly)(10)的自组装，而多肽与Gly到Ser的取代自结合形成了纤维状结构。
The process of self-assembly of the triple-helical peptide (Pro-Hyp-Gly)(10) into higher order structure resembles the nucleation-growth mechanism of collagen fibril formation in many features, but the irregular morphology of the self-assembled peptide contrasts with the ordered fibers and networks formed by collagen in vivo. The amino acid sequence in the central region of the (Pro-Hyp-Gly)(10) peptide was varied and found to affect the kinetics of self-assembly and nature of the higher order structure formed. Single amino acid changes in the central triplet produced irregular higher order structures similar to (Pro-Hyp-Gly)(10), but the rate of self-association was markedly delayed by a single change in one Pro to Ala or Leu. The introduction of a Hyp-rich hydrophobic sequence from type IV collagen resulted in a more regular suprastructure of extended fibers that sometimes showed supercoiling and branching features similar to those seen for type IV collagen in the basement membrane network. Several peptides, where central Pro-Hyp sequences were replaced by charged residues or a nine-residue hydrophobic region from type III collagen, lost the ability to self-associate under standard conditions. The inability to self-assemble likely results from loss of imino acids, and lack of an appropriate distribution of hydrophobic/electrostatic residues. The effect of replacement of a single Gly residue was also examined, as a model for collagen diseases such as osteogenesis imperfecta and Alport syndrome. Unexpectedly, the Gly to Ala replacement interfered with self-assembly of (Pro-Hyp-Gly)(10), while the peptide with a Gly to Ser substitution self-associated to form a fibrillar structure.