Fassina G, Chaiken I M
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
J Biol Chem. 1988 Sep 25;263(27):13539-43.
Site-specific, truncated, and sequence-simplified analogs of the hormone [Arg8]vasopressin were investigated for the relationship between their abilities to recognize immobilized bovine neurophysin and to promote neurophysin self-association. Peptide binding to neurophysin was measured quantitatively by analytical high performance affinity chromatography on immobilized bovine neurophysin II. Neurophysin self-association, measured as binding of soluble to immobilized neurophysin, was promoted (made higher affinity) by soluble peptide hormone and its analogs, with the effect of particular peptides being proportional to their binding affinities for neurophysin. Sequence-redesigned peptides able to recognize neurophysin, including dipeptide amides, were able to potentiate the self-association to the same extent as the natural hormone when tested at concentrations adjusted to effect equal degrees of saturation of neurophysin. The relationship between peptide affinity to neurophysin and the potentiation of self-association suggests that the latter is directly dependent on the former and can occur even with limited segments of hormone sequence. The data fit best to a model in which hormone binding and self-association surfaces of neurophysin are separate and linked through the neurophysin molecule to produce cooperativity (hormone-promoted self-association). Given that only limited structural elements of hormone are required for promoting self-association, the results fit less well with models in which cooperativity requires that hormone make dimer-stabilizing contacts with both self-associating subunits of neurophysin simultaneously.
研究了激素[精氨酸8]加压素的位点特异性、截短型和序列简化类似物，以探讨它们识别固定化牛神经垂体素的能力与促进神经垂体素自缔合之间的关系。通过在固定化牛神经垂体素II上进行分析型高效亲和色谱法定量测定肽与神经垂体素的结合。以可溶性神经垂体素与固定化神经垂体素的结合来衡量神经垂体素的自缔合，可溶性肽激素及其类似物可促进（使其亲和力更高）这种自缔合，特定肽的作用与其对神经垂体素的结合亲和力成正比。在调整浓度以实现神经垂体素同等程度饱和的情况下进行测试时，能够识别神经垂体素的序列重新设计的肽，包括二肽酰胺，能够与天然激素一样程度地增强自缔合。肽对神经垂体素的亲和力与自缔合增强之间的关系表明，后者直接依赖于前者，即使激素序列片段有限也可能发生。数据最符合这样一种模型，即神经垂体素的激素结合表面和自缔合表面是分开的，并通过神经垂体素分子相连以产生协同作用（激素促进的自缔合）。鉴于促进自缔合仅需要激素的有限结构元件，因此结果与协同作用要求激素同时与神经垂体素的两个自缔合亚基形成二聚体稳定接触的模型不太相符。
