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GLYCOPROTEIN HORMONE RECEPTOR MUTATIONS

机译:糖蛋白激素受体突变

摘要

A mutant thyroid stimulating hormone receptor (TSHR) or fragment thereof comprises one or more mutations, wherein the mutant TSHR has increased thermostability with respect to the equivalent wild type TSHR or fragment. The one or more mutation is preferably within the extracellular leucine-rich repeat domain (LRD) of the TSHR, or within residues 22 to 260 (TSHR260) of the TSHR, or may be in the transmembrane domain (TMD), A mutant TSHR or fragment thereof of the invention preferably consists of, or consists essentially of, the subdomain TSHR260 of the TSHR receptor. A mutant TSHR or fragment thereof according to the invention has a greater thermostability than the equivalent wild type TSHR or fragment as determined by its half-life at a given temperature, and can be purified whilst retaining activity. A mutant TSHR or fragment thereof according to the invention may also be deglycosylated whilst retaining activity. Methods, kits and uses employing the mutant TSHR or fragment thereof according to the invention are also provided.
机译:突变体甲状腺刺激激素受体(TSHR)或其片段包含一种或多种突变,其中突变体TSHR相对于当量的野生型TSHR或片段具有增加的热稳定性。一个或多个突变优选在TSHR的细胞外亮氨酸富含量的重复域(LRD)内,或者在TSHR的残基22-260(TSHR260)内,或者可以在跨膜结构域(TMD)中,突变TSHR或本发明的片段优选由TSHR受体的子域TSHR260基本上由或基本上组成。根据本发明的突变体Tshr或其片段具有比其半衰期在给定温度下确定的等效野生型Tshr或片段更大的热稳定性,并且可以在保持活性的同时纯化。根据本发明的突变Tshr或其片段也可以进行脱糖基,而保持活性。还提供了使用根据本发明的突变TSHR或其片段的方法,试剂盒和用途。

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