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凝血因子 IX 羧基末端区域中 Y450（c234）苯环的替换会对分泌和酶活性产生多效性影响。

Replacement of the Y450 (c234) phenyl ring in the carboxyl-terminal region of coagulation factor IX causes pleiotropic effects on secretion and enzyme activity.

机构信息

Department of Life Sciences and Biotechnology and LTTA Center, University of Ferrara, Ferrara, Italy.

出版信息

FEBS Lett. 2013 Oct 1;587(19):3249-53. doi: 10.1016/j.febslet.2013.08.019. Epub 2013 Aug 27.

DOI:10.1016/j.febslet.2013.08.019
PMID:23994528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3778434/
Abstract

The interplay between impaired protein biosynthesis and/or function caused by missense mutations, particularly in relation to specific protein regions, has been poorly investigated. As model we chose the severe p.Y450C mutation in the carboxyl-terminal region of coagulation factor IX (FIX) and, by expression of a panel of recombinant variants, demonstrated the key role of the tyrosine phenyl group for both FIX secretion and coagulant activity. Comparison among highly homologous coagulation serine proteases indicate that additive or compensatory pleiotropic effects on secretion and function by carboxyl-terminal mutations produce life-threatening or mild phenotypes in the presence of similarly reduced protein amounts.

摘要

错义突变导致的蛋白质生物合成和/或功能障碍之间的相互作用，特别是与特定蛋白质区域的关系，尚未得到充分研究。我们选择了凝血因子 IX (FIX) 羧基末端区域的严重 p.Y450C 突变作为模型，并通过一系列重组变体的表达，证明了酪氨酸苯环对于 FIX 分泌和凝血活性都具有关键作用。对高度同源的凝血丝氨酸蛋白酶的比较表明，羧基末端突变对分泌和功能的累加或补偿性多效性效应会导致在蛋白质数量相似减少的情况下产生危及生命或轻度的表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/74c6a56ba000/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/a32927b43ae9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/45d39c5d19f6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/74c6a56ba000/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/a32927b43ae9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/45d39c5d19f6/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15c/3778434/74c6a56ba000/gr3.jpg

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