Dissecting the structural and functional consequences of the evolutionary proline–glycine deletion in the wing 1 region of the forkhead domain of human FoxP1
IF 3.5 4区 生物学Q1 Biochemistry, Genetics and Molecular Biology
Stephanie Tamarín, Pablo Galaz-Davison, César A. Ramírez-Sarmiento, Jorge Babul, Exequiel Medina
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引用次数: 0
Abstract
The human FoxP transcription factors dimerize via three-dimensional domain swapping, a unique feature among the human Fox family, as result of evolutionary sequence adaptations in the forkhead domain. This is the case for the conserved glycine and proline residues in the wing 1 region, which are absent in FoxP proteins but present in most of the Fox family. In this work, we engineered both glycine (G) and proline–glycine (PG) insertion mutants to evaluate the deletion events in FoxP proteins in their dimerization, stability, flexibility, and DNA-binding ability. We show that the PG insertion only increases protein stability, whereas the single glycine insertion decreases the association rate and protein stability and promotes affinity to the DNA ligand.
人类 FoxP 转录因子通过三维结构域交换实现二聚化,这是人类 Fox 家族的一个独特特征,是叉头结构域进化序列适应性的结果。翼 1 区域的保守甘氨酸和脯氨酸残基就是这种情况,FoxP 蛋白中不存在这两个残基,但大多数 Fox 家族中都有。在这项工作中,我们设计了甘氨酸(G)和脯氨酸-甘氨酸(PG)插入突变体,以评估 FoxP 蛋白中的缺失事件对其二聚化、稳定性、灵活性和 DNA 结合能力的影响。我们发现,PG插入只增加了蛋白质的稳定性,而单甘氨酸插入则降低了结合率和蛋白质的稳定性,并提高了与DNA配体的亲和力。
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.