Ashman J B, Miller J
Committee on Immunology, University of Chicago, IL 60637, USA.
J Immunol. 1999 Sep 1;163(5):2704-12.
MHC class II and invariant chain (Ii) associate early in biosynthesis to form a nonameric complex. Ii first assembles into a trimer and then associates with three class II alphabeta heterodimers. Although the membrane-proximal region of the Ii luminal domain is structurally disordered, the C-terminal segment of the luminal domain is largely alpha-helical and contains a major interaction site for the Ii trimer. In this study, we show that the Ii transmembrane domain plays an important role in the formation of Ii trimers. The Ii transmembrane domain contains an unusual patch of hydrophilic residues near the luminal interface. Substitution of these polar residues with nonpolar amino acids resulted in a decrease in the efficiency of Ii trimerization and subsequent class II association. Moreover, N-terminal fragments of Ii were found to trimerize independently of the luminal alpha-helical domain. Progressive C-terminal truncations mapped a homotypic association site to the first 80 aa of Ii. Together, these results implicate the Ii transmembrane domain as a site of trimer interaction that can play an important role in the initiation of trimer formation.
主要组织相容性复合体II类分子（MHC class II）与恒定链（Ii）在生物合成早期结合形成九聚体复合物。Ii首先组装成三聚体，然后与三个II类αβ异二聚体结合。尽管Ii腔结构域的膜近端区域在结构上是无序的，但腔结构域的C末端片段主要是α螺旋结构，并且包含Ii三聚体的一个主要相互作用位点。在本研究中，我们表明Ii跨膜结构域在Ii三聚体的形成中起重要作用。Ii跨膜结构域在靠近腔界面处含有一片不寻常的亲水性残基。用非极性氨基酸取代这些极性残基导致Ii三聚化效率降低以及随后与II类分子的结合减少。此外，发现Ii的N末端片段可独立于腔α螺旋结构域进行三聚化。C末端的逐步截短将一个同型结合位点定位到Ii的前80个氨基酸。这些结果共同表明Ii跨膜结构域是三聚体相互作用的位点，在三聚体形成的起始过程中可发挥重要作用。
