Specificity of tissue transglutaminase explains cereal toxicity in celiac disease.
Specificity of tissue transglutaminase explains cereal toxicity in celiac disease.
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DOI：
10.1084/jem.20012028
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发表时间：
2002-03-04
期刊：
影响因子：
--
通讯作者：
Koning F
中科院分区：
文献类型：
--
作者：
Vader LW;de Ru A;van der Wal Y;Kooy YM;Benckhuijsen W;Mearin ML;Drijfhout JW;van Veelen P;Koning F
乳糜泻是由选择性缺乏T细胞对麸质的耐受性引起的。已知酶组织转氨酶（tTG）通过谷氨酰胺（谷蛋白中最丰富的氨基酸）的脱酰胺作用参与T细胞刺激性谷蛋白肽的产生。然而，只有特定的谷氨酰胺残基被tTG修饰。在这里，我们提供的证据表明，谷氨酰胺和脯氨酸，第二个最丰富的氨基酸在面筋之间的间距，脱酰胺的特异性起着至关重要的作用。在此基础上，设计了预测面筋蛋白中新型T细胞刺激肽的算法。引人注目的是，这些算法在来自大麦的谷蛋白样醇溶蛋白和来自黑麦的黑麦蛋白中鉴定出许多相似的肽，但在来自燕麦的燕麦蛋白中没有。燕麦蛋白含有显著较低百分比的脯氨酸残基，这为燕麦缺乏毒性提供了可能的解释。因此，大麦和黑麦中谷蛋白和相关蛋白的独特氨基酸组成有利于通过tTG产生毒性T细胞刺激性谷蛋白肽。这为观察到乳糜泻患者对这些谷物蛋白质不耐受而对其他常见食物蛋白质不耐受提供了理论基础。
Celiac disease is caused by a selective lack of T cell tolerance for gluten. It is known that the enzyme tissue transglutaminase (tTG) is involved in the generation of T cell stimulatory gluten peptides through deamidation of glutamine, the most abundant amino acid in gluten. Only particular glutamine residues, however, are modified by tTG. Here we provide evidence that the spacing between glutamine and proline, the second most abundant amino acid in gluten, plays an essential role in the specificity of deamidation. On the basis of this, algorithms were designed and used to successfully predict novel T cell stimulatory peptides in gluten. Strikingly, these algorithms identified many similar peptides in the gluten-like hordeins from barley and secalins from rye but not in the avenins from oats. The avenins contain significantly lower percentages of proline residues, which offers a likely explanation for the lack of toxicity of oats. Thus, the unique amino acid composition of gluten and related proteins in barley and rye favors the generation of toxic T cell stimulatory gluten peptides by tTG. This provides a rationale for the observation that celiac disease patients are intolerant to these cereal proteins but not to other common food proteins.
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影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
DOI：
10.1084/jem.178.1.187
发表时间：
1993-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lundin KE;Scott H;Hansen T;Paulsen G;Halstensen TS;Fausa O;Thorsby E;Sollid LM
通讯作者：
Sollid LM
影响因子：
24.5
作者：
Janatuinen, EK;Kemppainen, TA;Mäki, M
通讯作者：
Mäki, M
影响因子：
158.5
作者：
JANATUINEN, EK;PIKKARAINEN, PH;JULKUNEN, RJK
通讯作者：
JULKUNEN, RJK
影响因子：
--
作者：
Spurkland, A;Ingvarsson, G;Thorsby, E
通讯作者：
Thorsby, E