Mutations in specific I-A(k) alpha(2) and beta(2) domain residues affect surface expression.
Mutations in specific I-A(k) alpha(2) and beta(2) domain residues affect surface expression.
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特定 I-A(k) alpha(2) 和 beta(2) 结构域残基的突变会影响表面表达。
DOI：
10.1093/intimm/12.6.777
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发表时间：
2000
影响因子：
4.4
通讯作者：
Wade,WF
中科院分区：
文献类型：
--
作者：
Lang,ML;Yadati,S;Seeley,ES;Nydam,T;Wade,TK;Gabriel,JL;Yeaman,G;Barisas,BG;Wade,WF
A previous investigation demonstrated that several mutations in class II dimer-of-dimers contact residues interfere with antigen presentation by transfectants but not with plasma membrane expression of the mutant class II. In the present study we examined other class II mutations in this region thatdidinhibit plasma membrane expression of mutant class II molecules. Molecules containing both mutations Hα181D in the α2domain and Eβ170K in the β2domain exhibited low plasma membrane expression, but molecules with only one of these mutations were expressed normally. The mutant class II molecules were transported to organelles that were accessible to a fluid-phase protein, hen egg lysozyme (HEL). Culture of transfectants with lysozyme enhanced the amount of class II compact dimer (αβ plus peptide; CD), and this was especially marked for the class II mutant Hα181D/Eβ170K and for other molecules possessing both mutations. Formation of class II CD was not paralleled by an increase in class II surface expression. Thus the joint mutation of Hα181 and Eβ170 has two effects. In the absence of high concentrations of exogenous peptide, it prevents efficient CD formation, possibly by affecting invariant chain (Ii) proteolysis and/or the stability of the class II after Ii/CLIP is removed. At high peptide concentrations supplied by exogenous HEL, the mutations allow CD formation, but not expression of class II on the plasma membrane. Molecular modeling of the possible interaction of class II and Ii suggests that the mutant amino acids Hα181D and Eβ170K, besides affecting the overall stability of class II, might also interact with Ii via two loops in class II's α2and β2domains respectively.
