通过X射线和中子溶液散射对人补体成分C4及其片段进行分子建模。
Molecular modeling of human complement component C4 and its fragments by X-ray and neutron solution scattering.
作者信息
Perkins S J, Nealis A S, Sim R B
机构信息
Department of Biochemistry and Chemistry, Royal Free Hospital School of Medicine, London, U.K.
出版信息
Biochemistry. 1990 Feb 6;29(5):1167-75. doi: 10.1021/bi00457a011.
The solution structures of human complement component C4 and five derived fragments, C4u, C4(a + b), C4b, C4c, and C4d, were analyzed by synchrotron X-ray and neutron scattering. The X-ray radii of gyration RG for C4, C4u, and C4(a + b) in H2O buffers are similar at 5.23-5.28 nm, and likewise the cross-sectional radii of gyration RXS are similar at 2.48-2.52 nm. Molecular mass calculations using X-rays and neutrons show unexpectedly that C4c is dimeric; however, all the other forms are monomeric. C4c2 has an X-ray RG of 5.18 nm and an RXS of 2.89 nm. Neutron contrast variation gives RG values at infinite contrast of 4.87-4.93 nm for C4 and C4u, 4.79 nm for C4b, 4.94 nm for C4c2, and 2.69 nm for C4d. The RXS values at infinite contrast are 2.23-2.25 nm for C4 and C4u, 1.89 nm for C4b, and 2.62 nm for C4c2. These data show that a large conformational change occurs on going from C4 to C4b, but not on going from C4 to C4u, and this is attributed to the presence of the C4a moiety in C4u. Comparisons of the C4 and C4u scattering curves show that these are very similar out to a nominal resolution of 4 nm. Scattering-curve models were developed to account for the neutron scattering curves of C4, C4c2, and C4d in 2H2O buffers. The C4c monomer could be represented by a lamellar ellipsoid of size 8 nm x 2 nm x 18 nm. C4d was found to be 4 nm x 2 nm x 9 nm. The combination of these structures gave good accounts of the neutron data for C4, C4b, and C4c2 to resolutions of 5-6 nm. The C4 model was obtained by placing the long axis of C4d parallel to that of C4c such that the cross section is extended. C4b was best modeled by repositioning C4d relative to C4c such that this cross section becomes more compact. The C4 and C4b models are compared with possible structures for the C1 component of complement to show the importance of the surface accessibility of the protease domains and short consensus repeat domains in C1 for C4 activation.
通过同步加速器X射线和中子散射分析了人补体成分C4及其五个衍生片段C4u、C4(a + b)、C4b、C4c和C4d的溶液结构。在H2O缓冲液中，C4、C4u和C4(a + b)的X射线回转半径RG相似，为5.23 - 5.28 nm，同样，截面回转半径RXS也相似，为2.48 - 2.52 nm。使用X射线和中子进行的分子量计算意外地表明C4c是二聚体；然而，所有其他形式都是单体。C4c2的X射线RG为5.18 nm，RXS为2.89 nm。中子对比度变化给出了在无限对比度下C4和C4u的RG值为4.87 - 4.93 nm，C4b为4.79 nm，C4c2为4.94 nm，C4d为2.69 nm。在无限对比度下，C4和C4u的RXS值为2.23 - 2.25 nm，C4b为1.89 nm，C4c2为2.62 nm。这些数据表明，从C4到C4b发生了大的构象变化，但从C4到C4u则没有，这归因于C4u中存在C4a部分。C4和C4u散射曲线的比较表明，在名义分辨率为4 nm之前，它们非常相似。开发了散射曲线模型来解释2H2O缓冲液中C4、C4c2和C4d的中子散射曲线。C4c单体可以用尺寸为8 nm×2 nm×18 nm的层状椭球体表示。发现C4d为4 nm×2 nm×9 nm。这些结构的组合很好地解释了C4、C4b和C4c2在5 - 6 nm分辨率下的中子数据。通过将C4d的长轴与C4c的长轴平行放置，使截面扩展，得到了C4模型。通过相对于C4c重新定位C4d，使该截面变得更紧凑，从而对C4b进行了最佳建模。将C4和C4b模型与补体C1成分的可能结构进行比较，以显示C1中蛋白酶结构域和短共有重复结构域的表面可及性对C4激活的重要性。
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