Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs.
Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs.
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DOI：
10.1093/glycob/cwn073
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发表时间：
2008-11
期刊：
影响因子：
4.3
通讯作者：
Jamison O
中科院分区：
文献类型：
--
作者：
Gerken TA;Ten Hagen KG;Jamison O
UDP-GalNAc：多肽α- n-乙酰半乳糖氨基转移酶（ppGalNAc Ts）包含一个大家族的糖基转移酶，启动粘蛋白型蛋白的o糖基化，将α-GalNAc转移到多肽受体的Thr和Ser残基上。ppGalNAc t家族存在于从哺乳动物到单细胞生物的各种真核生物中。个体ppGalNAc T家族成员的肽底物特异性和特异性蛋白靶点仍然知之甚少。之前，我们报道了一系列定向随机肽底物库，用于定量测定哺乳动物ppGalNAc T1和T2的肽底物特异性。通过这些底物，揭示了转移酶以前未知的特征。利用这些和一组新的延长的随机肽，现在已经对果蝇T1和T2的同源基因PGANT5和PGANT2进行了研究。这些研究的结果表明，这些转移酶的主要肽底物决定因素包含在糖基化位点两侧的2至3个残基中。研究进一步发现，哺乳动物和苍蝇的T1同源物显示出非常相似的肽底物偏好，而T2同源物几乎无法区分，这表明在整个进化过程中，同源对之间保持了相似的肽偏好。这一结论进一步得到了每个转移酶同源物序列同源性比较的支持，表明肽底物和UDP结合位点残基相对于其剩余的催化和凝集素结构域残基在物种之间具有更高的保守性。
UDP-GalNAc: polypeptide α-N-acetylgalactosaminyltransferases (ppGalNAc Ts) comprise a large family of glycosyltransferases that initiate mucin-type protein O-glycosylation, transferring α-GalNAc to Thr and Ser residues of polypeptide acceptors. Families of ppGalNAc Ts are found across diverse eukaryotes with orthologues identifiable from mammals to single cell organisms. The peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remains poorly understood. Previously, we reported a series of oriented random peptide substrate libraries for quantitatively determining the peptide substrate specificities of the mammalian ppGalNAc T1 and T2. With these substrates, previously unknown features of the transferases were revealed. Utilizing these and a new lengthened set of random peptides, studies have now been performed on PGANT5 and PGANT2, the Drosophila orthologues of T1 and T2. The results from these studies suggests that the major peptide substrate determinants for these transferases is contained within 2 to 3 residues flanking the site of glycosylation. It is further found that the mammalian and fly T1 orthologues display very similar peptide substrate preferences, while the T2 orthologues are nearly indistinguishable, suggesting similar peptide preferences amongst orthologous pairs have been maintained across evolution. This conclusion is further supported by sequence homology comparisons of each of the transferase orthologues, showing that the peptide substrate and UDP binding site residues are more highly conserved between species relative to their remaining catalytic and lectin domain residues.
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DOI：
10.1073/pnas.0705984104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Lang, Tiange;Hansson, Gunnar C.;Samuelsson, Tore
通讯作者：
Samuelsson, Tore
影响因子：
4.8
作者：
Raman, Jayalakshmi;Fritz, Timothy A.;Tabak, Lawrence A.
通讯作者：
Tabak, Lawrence A.
影响因子：
2.9
作者：
Gerken, TA;Tep, C;Rarick, J
通讯作者：
Rarick, J
影响因子：
4
作者：
Freire, T;Casaravilla, C;Osinaga, E
通讯作者：
Osinaga, E
影响因子：
4.8
作者：
Gerken, TA;Zhang, JX;Elhammer, Å
通讯作者：
Elhammer, Å