肽转运载体的分子特征及其分布

动物体内的肽转运载体目前发现的至少有五种,其中研究最为广泛的是：PepT1和PepT2。PepT1和PepT2都是依质子的寡肽转运载体(POT)家族的成员。PepT1是低亲和力／高容量的肽载体,PepT2高亲和力／低容量的肽载体。PepT1主要在消化道中表达,在肾脏中也有微弱的表达;PepT2主要在肾脏中表达。这些肽载体的分子结构特征主要有：(1)有12个假想的穿膜区,在9区和10区之间有一大的胞外环,且所有穿膜区内的序列都高度保守,胞外环上的序列保守的很少;(2)被编码的蛋白上有多个N-糖基化和蛋白激酶的识别位点,它们可能参与肽转运的调控;(3)PepT1上的His-57和PepT2上的His-87是最关键的组氨酸残基,它们可能是转运蛋白发挥吸收功能时最关键的结合位点;(4)不同动物肽转运蛋白的氨基酸范围在707到729之间,且不同动物相同器官肽转运载体的同源性高(大约80％),同种动物不同器官肽转运载体的同源性低(大约50％)。了解肽载体的分子特征和组织分布,可以更好地理解肽吸收的分子机制并有利于肽类药物的研发。

Molecular characteristics and tissue distribution of peptide transporters

At present, there are at least five kinds of peptide transporters identified in animal tissues, in which PepT1 and PepT2 were discussed most extensively. PepT1 and PepT2 are all members of proton-dependent oligopeptide transporters(POT) family. PepT1 is peptide transporter of low affinity and high capacity whereas PepT2 is high affinity and low capacity. PepT1 is mainly expressed in intestinal tract and weakly expressed in kidney, but PepT2 is mainly expressed in kidney. These transporters have some significant molecular characteristics: (1) Contain 12 membrane-spanning domains and a large extracellular loop between transmembrane domains 9 and 10, and all of the transmenbrane domains are highly conserved, the extracellular loops are much less so; (2) The encoded proteins have a number of potential N-glycosylation as well as protein kinase recognition sites, which may be involved in the regulation of peptide transport; (3) His-57 in PepT1 and His-87 in PepT2 are the most critical histidyl residues that are necessary for the uptake function and probably represent some critical binding sites; (4) The proteins range in size from 707 to 729 amino acid residues in various species, with higher homology between species for a given transporter (approximately 80%) and less homology between transporters for a given species(approximately 50%). With the knowledge of the molecular characteristics and tissue distribution of these peptide transporters, we can understand the molecular mechanism underlying the peptide absorption, which may improve the peptide-drugs development in the future.