Structure of a Classical MHC Class I Molecule That Binds "Non-Classical" Ligands
Structure of a Classical MHC Class I Molecule That Binds "Non-Classical" Ligands
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DOI：
10.1371/journal.pbio.1000557
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发表时间：
2010-12-01
期刊：
影响因子：
9.8
通讯作者：
Ziegler, Andreas
中科院分区：
文献类型：
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作者：
Hee, Chee Seng;Gao, Song;Ziegler, Andreas
鸡YF 1基因与经典的MHC I类基因座有着密切的序列关系，但位于核心MHC区域之外。为了深入了解它们的功能，我们通过X射线晶体学在1.3埃分辨率下确定了YF 1 *7.1/β（2）-微球蛋白复合物的结构。它表现出典型的经典MHC I类分子的结构，但具有含有非肽配体的疏水结合沟。这一发现促使我们也用各种自身脂质重建YF 1 *7.1。解决了另外七个YF 1 *7.1结构，但只有聚乙二醇分子可以建模为结合沟内的电子密度。然而，通过天然等电聚焦对YF 1 *7.1的评估表明，该分子也能够结合非自身脂质。YF 1 *7.1与疏水配体相互作用的能力在经典的MHC I类蛋白中是前所未有的，并且可能有助于鸡免疫系统识别具有最少数量的MHC I类分子的多种配体库。
Chicken YF1 genes share a close sequence relationship with classical MHC class I loci but map outside of the core MHC region. To obtain insights into their function, we determined the structure of the YF1*7.1/beta(2)-microgloblin complex by X-ray crystallography at 1.3 angstrom resolution. It exhibits the architecture typical of classical MHC class I molecules but possesses a hydrophobic binding groove that contains a non-peptidic ligand. This finding prompted us to reconstitute YF1*7.1 also with various self-lipids. Seven additional YF1*7.1 structures were solved, but only polyethyleneglycol molecules could be modeled into the electron density within the binding groove. However, an assessment of YF1*7.1 by native isoelectric focusing indicated that the molecules were also able to bind nonself-lipids. The ability of YF1*7.1 to interact with hydrophobic ligands is unprecedented among classical MHC class I proteins and might aid the chicken immune system to recognize a diverse ligand repertoire with a minimal number of MHC class I molecules.