Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules.
Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules.
复制标题
淀粉样前体样蛋白 2 与 MHC I 类分子相互作用的特异性。
DOI：
10.1007/s00251-008-0296-0
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发表时间：
2008
期刊：
影响因子：
3.2
通讯作者：
Solheim,JoyceC
中科院分区：
文献类型：
--
作者：
Tuli,Amit;Sharma,Mahak;Naslavsky,Naava;Caplan,Steve;Solheim,JoyceC
广泛表达的淀粉样蛋白受体样蛋白2（APLP 2）以前被发现调节主要组织相容性复合体（MHC）I类分子Kd的细胞表面表达并与Kd强烈结合。在这里报道的研究中，我们证明了APLP 2在不同程度上与其他几种小鼠MHC I类同种异型结合，并且APLP 2影响MHC I类分子的细胞表面表达的能力不限于Kd。Ld与Kd一样，与高尔基体中的APLP 2相关，但Kd也与胞内囊泡结构中的APLP 2相关。我们还研究了β 2 m对APLP 2/MHC相互作用的影响，发现人β 2 m转染增加了APLP 2与小鼠MHC I类分子的结合，可能是通过影响H2 I类重链构象。APLP 2被证明与具有折叠外结构域的Ld构象特异性结合，这与我们先前关于Kd的结果一致，表明APLP 2与这些H2 I类分子中的每一个上的α1α2区域相互作用。此外，我们观察到与APLP 2的结合涉及MHC α3/跨膜/胞质区域，这表明H2 I类分子的保守和多态性区域可能参与与APLP 2的相互作用。总之，我们证明了APLP 2的结合、共定位模式和功能影响在H2 I类分子中是不同的，并且APLP 2/MHC缔合受到MHC I类重链的多个结构域和β 2 m对重链构象的影响。
The ubiquitously expressed amyloid precursor-like protein 2 (APLP2) has been previously found to regulate cell surface expression of the major histocompatibility complex (MHC) class I molecule Kdand bind strongly to Kd. In the study reported here, we demonstrated that APLP2 binds, in varied degrees, to several other mouse MHC class I allotypes and that the ability of APLP2 to affect cell surface expression of an MHC class I molecule is not limited to Kd. Ld, like Kd, was found associated with APLP2 in the Golgi, but Kdwas also associated with APLP2 within intracellular vesicular structures. We also investigated the effect of β2m on APLP2/MHC interaction and found that human β2m transfection increased the association of APLP2 with mouse MHC class I molecules, likely by affecting H2 class I heavy chain conformation. APLP2 was demonstrated to bind specifically to the conformation of Ldhaving folded outer domains, consistent with our previous results with Kdand indicating APLP2 interacts with the α1α2 region on each of these H2 class I molecules. Furthermore, we observed that binding to APLP2 involved the MHC α3/transmembrane/cytoplasmic region, suggesting that conserved as well as polymorphic regions of the H2 class I molecule may participate in interaction with APLP2. In summary, we demonstrated that APLP2’s binding, co-localization pattern, and functional impact vary among H2 class I molecules and that APLP2/MHC association is influenced by multiple domains of the MHC class I heavy chain and by β2m’s effects on the conformation of the heavy chain.