Shire S J, Holladay L A, Rinderknecht E
Department of Pharmaceutical Research and Development, Genentech, Inc., South San Francisco, California 94080.
Biochemistry. 1991 Aug 6;30(31):7703-11. doi: 10.1021/bi00245a006.
The self-association properties of recombinant DNA derived human relaxin, and porcine relaxin isolated from porcine ovaries, have been studied by sedimentation equilibrium analytical ultracentrifugation and circular dichroism (CD). The human relaxin ultracentrifuge data were adequately defined by a monomer-dimer self-association model with an association constant of approximately 6 x 10(5) M-1, whereas porcine relaxin was essentially monomeric in solution. An approximate 5-fold increase in weight fraction of human relaxin monomer elicited by dilution of the protein resulted in no change in the far-UV CD spectrum at 220 nm. In contrast, after the same increase in weight fraction of monomer, the near-UV circular dichroism spectra for human relaxin exhibited a significant decrease in the amplitude for the CD bands near 277 and 284 nm. These CD bands, which may be assigned to the lone tyrosine in human relaxin, are superimposed on a broad envelope that is probably due to the three disulfide chromophores. Although both the human and porcine proteins contain two tryptophan residues, the near-UV CD spectra exhibit only a broad shoulder near 295 nm rather than the strong CD bands often found for tryptophan. Moreover, there is little change in this broad band after dilution of human relaxin to concentrations that resulted in a 4-fold increase in monomer weight fraction. These data suggest that dissociation of the human relaxin dimer to monomer is not accompanied by large overall changes in secondary structure or alteration in the average tryptophan environment, whereas there is a significant change in the tyrosine environment.(ABSTRACT TRUNCATED AT 250 WORDS)
通过沉降平衡分析超速离心和圆二色性(CD)研究了重组DNA衍生的人松弛素以及从猪卵巢中分离出的猪松弛素的自缔合特性。人松弛素的超速离心数据可以用单体-二聚体自缔合模型充分描述,缔合常数约为6×10⁵ M⁻¹,而猪松弛素在溶液中基本以单体形式存在。蛋白质稀释引起人松弛素单体重量分数约5倍的增加,在220 nm处远紫外CD光谱没有变化。相反,单体重量分数同样增加后,人松弛素的近紫外圆二色性光谱在277和284 nm附近的CD带振幅显著降低。这些CD带可能归属于人松弛素中的单个酪氨酸,叠加在一个宽包络上,这可能是由于三个二硫键发色团引起的。尽管人和猪的蛋白质都含有两个色氨酸残基,但近紫外CD光谱仅在295 nm附近显示一个宽肩,而不是色氨酸常见的强CD带。此外,将人松弛素稀释到导致单体重量分数增加4倍的浓度后,这个宽带几乎没有变化。这些数据表明,人松弛素二聚体解离为单体时,二级结构没有大的整体变化,色氨酸平均环境也没有改变,而酪氨酸环境有显著变化。(摘要截短至250字)