Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
Biomacromolecules. 2017 Feb 13;18(2):617-624. doi: 10.1021/acs.biomac.6b01808. Epub 2017 Jan 18.
Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present. Here we present mutations to a composition- and register-controlled AAB helix where one of the requisite glycines in the A chain of the triple helix is changed to serine or alanine. We see a loss of compositional control when the A chain is mutated, resulting in an A'BB composition that minimizes the number of mutations included in the triple helix. However, when both A and B chains are mutated and no nonmutated peptide chains are available, the designed A'A'B' composition is reestablished. Our work shows the ability of the mutations to influence and alter the composition and register of the collagen triple helix.
成骨不全症通常是由于胶原蛋白基因组中的错义突变引起的，其中所需的甘氨酸残基被另一种氨基酸取代。许多模型都试图在三螺旋水平上复制突变胶原的结构。然而，三螺旋的组成和登记控制很复杂，需要极高的精度，尤其是在存在这些不稳定突变的情况下。在这里，我们提出了对组成和登记控制的 AAB 螺旋的突变，其中三螺旋 A 链中的一个必需甘氨酸被丝氨酸或丙氨酸取代。当 A 链发生突变时，我们看到组成控制的丧失，导致 A'BB 组成，最大限度地减少了三螺旋中包含的突变数量。然而，当 A 链和 B 链都发生突变且没有可用的非突变肽链时，设计的 A'A'B'组成得以重新建立。我们的工作表明，突变能够影响和改变胶原三螺旋的组成和登记。
