영어 문장 해석 부탁드려요
-
게시물 수정 , 삭제는 로그인 필요
2.2.2 proline hydroxylation and Oglycosylation of hydroxyproline(Hyp)
Hydroxylation of Pro residues is often a prerequisite for protein Oglycosylation in plants. However, some hydroxyproline residues found in cell wall protein such as those in extensions and Hyprich glycoproteins(HRGPs), or in vacuolar proteins such as tobacco class I chitinase or sweet potato sporamin, are not glycosylated. Oglycosylation of Hyp is unique to plants, but proline hydroxylation also occurs in mammalian proteins such as collagens. In type I human collagen, about half of the Pro residues in the Y position of the GlyXY triplet are converted to Hyp within the lumen of the ER by the enzyme prolyl4hydroxylase. Prohydroxylation plays a central role in the triple helix formation of collagen, and the high content of Hyp increases the thermal stability of this molecule. Collagens are widely exploited molecules for medical use, cosmetics and therapeutics, and recombinant collagens have been expressed in various heterologous systems including plants.
Plants and mammals contain a prolyl4hydroxylase, but the sequence specificity of plant prolyl4hydroxylase differs markedly from the code that mammalian prolylhydroxylase recognize. As a result, the proline residues of type I human collagen produced in transgenic tobacco plants are not hydroxylated, and plantmade collagen shows increased flexibility as well as reduced melting temperature compared with the native molecule. An important progress concerning the quality and comformity of collagen from plants was made when type I human collagen was expressed together with an animal prolyl4hydroxylase in tobacco.
One of the best examples of plant proteins Oglycosylated on Hyp residues are Hyprich glycoproteins. HRGPs are located either in the cell wall or at the outer surface of the plasma membrane, where they represent the major surface glycoproteins in plants. The extent and type of Oglycosylation define three major HRGPs families, namely the repetitive prolinerich proteins, the extensins, and the arabinogalactan proteins, or AGPs. AGPs are hyperglycosylated, with two main type of Oglycosylation occurring on their Hyp residues(Fig. 2E): arabinosylation adding short,4-6 residues oligoarabinoside chains, and galactosylation adding larger, 30-150 residues acidic or neutral arabinogalactan polysaccharides. Glycosylation of Hyp is a complex mechanism first involving, once the protein is synthesized and translocated into the ER lumen conversion of selected Pro residues to Hyp residues by the action of prolyl4hydroxylase, either in the ER and/or in the Golgi apparatus. The next step is the transfer of a glycan from the donor substrate to the acceptor Hyp residue. Recent results favor the hypothesis stating that when AGP molecules arrive to the Golgi apparatus, cluster og Hyp residues in their primary structure are the sites of attachment for oligoarabinoside chains, whereas non contiguous Hyp would be the sites for arabinogalactan polysaccharide addition. Although one cannot rule out that the donor substrates for arabinogalactan polysaccharide sidechains addition are sugar nucleotides as for Oglycosylation in mammals, another possibility is the bulk transfer of a preassembled oligosaccharide moiety from a lipidlinked arabinogalactan precursor to Hyp residues.
Suprisingly, very little attention has been paid up to now to the Oglycosylation status of therapeutic proteins produced in transgenic plants. Based on current knowledge on this posttranslational modification, it is not possible to predict whether or not a therapeutic protein of mammalian origin, containing glycans Olinked to Thr/Ser residues, will be correctly Oglycosylated when produced in a plant expression system. However considering the wall known immunogenicity of HRGPtype Oglycans and their strong reactivity with Galspecific lectins such as Ricinus communis agglutinin, it can be anticipated that the presence of this type of oligosaccharide structure on a plantmade pharmaceutical would lead to accelerated clearance from the blood, both via carbohydrate specific antibodies and asialoglycoprotein receptors at the surface of hepatocytes.
2.2.2 proline hydroxylation and Oglycosylation of hydroxyproline(Hyp)
Hydroxylation of Pro residues is often a prerequisite for protein Oglycosylation in plants. However, some hydroxyproline residues found in cell wall protein such as those in extensions and Hyprich glycoproteins(HRGPs), or in vacuolar proteins such as tobacco class I chitinase or sweet potato sporamin, are not glycosylated. Oglycosylation of Hyp is unique to plants, but proline hydroxylation also occurs in mammalian proteins such as collagens. In type I human collagen, about half of the Pro residues in the Y position of the GlyXY triplet are converted to Hyp within the lumen of the ER by the enzyme prolyl4hydroxylase. Prohydroxylation plays a central role in the triple helix formation of collagen, and the high content of Hyp increases the thermal stability of this molecule. Collagens are widely exploited molecules for medical use, cosmetics and therapeutics, and recombinant collagens have been expressed in various heterologous systems including plants.
Plants and mammals contain a prolyl4hydroxylase, but the sequence specificity of plant prolyl4hydroxylase differs markedly from the code that mammalian prolylhydroxylase recognize. As a result, the proline residues of type I human collagen produced in transgenic tobacco plants are not hydroxylated, and plantmade collagen shows increased flexibility as well as reduced melting temperature compared with the native molecule. An important progress concerning the quality and comformity of collagen from plants was made when type I human collagen was expressed together with an animal prolyl4hydroxylase in tobacco.
One of the best examples of plant proteins Oglycosylated on Hyp residues are Hyprich glycoproteins. HRGPs are located either in the cell wall or at the outer surface of the plasma membrane, where they represent the major surface glycoproteins in plants. The extent and type of Oglycosylation define three major HRGPs families, namely the repetitive prolinerich proteins, the extensins, and the arabinogalactan proteins, or AGPs. AGPs are hyperglycosylated, with two main type of Oglycosylation occurring on their Hyp residues(Fig. 2E): arabinosylation adding short,4-6 residues oligoarabinoside chains, and galactosylation adding larger, 30-150 residues acidic or neutral arabinogalactan polysaccharides. Glycosylation of Hyp is a complex mechanism first involving, once the protein is synthesized and translocated into the ER lumen conversion of selected Pro residues to Hyp residues by the action of prolyl4hydroxylase, either in the ER and/or in the Golgi apparatus. The next step is the transfer of a glycan from the donor substrate to the acceptor Hyp residue. Recent results favor the hypothesis stating that when AGP molecules arrive to the Golgi apparatus, cluster og Hyp residues in their primary structure are the sites of attachment for oligoarabinoside chains, whereas non contiguous Hyp would be the sites for arabinogalactan polysaccharide addition. Although one cannot rule out that the donor substrates for arabinogalactan polysaccharide sidechains addition are sugar nucleotides as for Oglycosylation in mammals, another possibility is the bulk transfer of a preassembled oligosaccharide moiety from a lipidlinked arabinogalactan precursor to Hyp residues.
Suprisingly, very little attention has been paid up to now to the Oglycosylation status of therapeutic proteins produced in transgenic plants. Based on current knowledge on this posttranslational modification, it is not possible to predict whether or not a therapeutic protein of mammalian origin, containing glycans Olinked to Thr/Ser residues, will be correctly Oglycosylated when produced in a plant expression system. However considering the wall known immunogenicity of HRGPtype Oglycans and their strong reactivity with Galspecific lectins such as Ricinus communis agglutinin, it can be anticipated that the presence of this type of oligosaccharide structure on a plantmade pharmaceutical would lead to accelerated clearance from the blood, both via carbohydrate specific antibodies and asialoglycoprotein receptors at the surface of hepatocytes.
#영어 문장 #영어 문장 분석 사이트 #영어 문장 교정 사이트 #영어 문장 형식 #영어 문장 검사기 #영어 문장성분 #영어 문장 구조 #영어 문장 1000개 #영어 문장 모음 #영어 문장 형식 분석기
