首页> 外文会议>International Symposium on Amyloidosis >CHARACTERIZATION OF POST-TRANSLATIONAL MODIFICATIONS OF AN AMYLOIDOGENIC IMMUNOGLOBULIN KAPPA LIGHT CHAIN BY MASS SPECTROMETRY
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CHARACTERIZATION OF POST-TRANSLATIONAL MODIFICATIONS OF AN AMYLOIDOGENIC IMMUNOGLOBULIN KAPPA LIGHT CHAIN BY MASS SPECTROMETRY

机译:淀粉样蛋白免疫球蛋白Kappa轻链的翻译后修饰的表征通过质谱法

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It has been shown that reduced folding stability is a unifying property of amyioidogenic immunogiobulin light chains. Amino acid replacements in the variable region and certain post-translational modifications (PTMs) can destabilize the folding state of the light chains and enable them to populate a partially unfolded intermediate state which may lead to fibril formation and organ damage (1). To have a better understanding of the role of Ig light chain modifications on amyloid deposition, we used a mass spectrometry (MS) based method to investigate amyioidogenic light chains from the urine of patients diagnosed with AL amyioidosis for detection of sequence variations and PTMs (2). In this study, a kappa 3 light chain (01-140) was characterized by MS and the identified modifications include an N-terminal oxidative deamination, asparagine deamidation,' tryptophan oxidation, S-sulfonation and the formation of a thiosulfonate linkage between an oxidized C-terminal Cys and a nearby Cys. About 92% of variable region sequence of this light chain was characterized de novo using tandem MS before genetic material and the cDNA sequence became available.
机译:已经表明,减少的折叠稳定性是玉米酰亚胺酰胺免疫导管轻链的统一性能。可变区和某些后翻版(PTMS)中的氨基酸替换可以使光链的折叠状态变得破坏并使它们能够填充部分展开的中间状态,这可能导致原纤维形成和器官损伤(1)。为了更好地理解IG轻链修饰对淀粉样蛋白沉积的作用,我们使用了基于质谱(MS)的方法来研究来自诊断患有Al乳糜胺中的患者尿液中的玉米酰亚胺灭菌链,以检测序列变异和PTMS(2 )。在该研究中,Kappa 3轻链(01-140)的特征在于MS,所鉴定的修饰包括N-末端氧化脱氨基,天冬酰胺脱氨酸,'色氨酸氧化,S-磺化和氧化硫酸硫酸盐键的形成。 C-Terminal Cys和附近的Cys。在遗传物质前使用串联MS,在遗传物质和CDNA序列中可获得约92%的这种轻链的可变区序列的逐诺。

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