Braks J A, Guldemond K C, van Riel M C, Coenen A J, Martens G J
Department of Animal Physiology, University of Nijmegen, The Netherlands.
FEBS Lett. 1992 Jun 22;305(1):45-50. doi: 10.1016/0014-5793(92)80652-w.
The multifunctional prohormone, proopiomelanocortin (POMC), is processed in the melanotrope cells of the pituitary pars intermedia at pairs of basic amino acid residues to give a number of peptides, including alpha-melanophore-stimulating hormone (alpha-MSH). This hormone causes skin darkening in amphibians during background adaptation. Here we report the complete structure of Xenopus laevis prohormone convertase PC2, the enzyme thought to be responsible for processing of POMC to alpha-MSH. A comparative structural analysis revealed an overall amino acid sequence identity of 85-87% between Xenopus PC2 and its mammalian counterparts, with the lowest degree of identity in the signal peptide sequence (28-36%) and the region amino-terminal to the catalytic domain (59-60%). The occurrence of a second, structurally different PC2 protein reflects the expression of two Xenopus PC2 genes. The expression pattern of PC2 in the Xenopus pituitary gland of black- and white-adapted animals was found to be similar to that of POMC, namely high expression in active melanotrope cells of black animals. This observation is in line with a physiological role for PC2 in processing POMC to alpha-MSH.
多功能激素原阿黑皮素原（POMC）在脑垂体中间部的黑素细胞中，于成对的碱性氨基酸残基处进行加工，生成多种肽，包括α-促黑素细胞激素（α-MSH）。这种激素在两栖动物适应背景环境时会导致皮肤变黑。在此，我们报告了非洲爪蟾促激素原转化酶PC2的完整结构，该酶被认为负责将POMC加工成α-MSH。比较结构分析显示，非洲爪蟾PC2与其哺乳动物对应物之间的整体氨基酸序列同一性为85%-87%，信号肽序列（28%-36%）和催化结构域氨基末端区域（59%-60%）的同一性程度最低。第二种结构不同的PC2蛋白的出现反映了非洲爪蟾两个PC2基因的表达。在适应黑色和白色环境的动物的非洲爪蟾脑垂体中，PC2的表达模式与POMC相似，即在黑色动物活跃的黑素细胞中高表达。这一观察结果与PC2在将POMC加工成α-MSH中的生理作用一致。
