Department of Biochemistry, Groupe de recherche axé sur la structure des protéines, McGill University, 3649 Promenade Sir William Osler, Montréal, Québec, Canada H3G 0B1.
J Mol Biol. 2010 Aug 27;401(4):618-25. doi: 10.1016/j.jmb.2010.06.045. Epub 2010 Jun 26.
Protein disulfide isomerases (PDIs) are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum (ER). The ER contains many different PDI-like proteins. Some, such as PDI, are general enzymes that directly recognize misfolded proteins while others, such as ERp57 and ERp72, have more specialized roles. Here, we report the high-resolution X-ray crystal structure of the N-terminal portion of ERp72 (also known as CaBP2 or PDI A4), which contains two a(0)a catalytic thioredoxin-like domains. The structure shows that the a(0) domain contains an additional N-terminal beta-strand and a different conformation of the beta5-alpha4 loop relative to other thioredoxin-like domains. The structure of the a domain reveals that a conserved arginine residue inserts into the hydrophobic core and makes a salt bridge with a conserved glutamate residue in the vicinity of the catalytic site. A structural model of full-length ERp72 shows that all three catalytic sites roughly face each other and positions the adjacent hydrophobic patches that are likely involved in protein substrate binding.
蛋白质二硫键异构酶（PDI）负责催化内质网（ER）中新生蛋白质中二硫键的正确氧化和异构化。内质网含有许多不同的 PDILike 蛋白。有些蛋白，如 PDI，是直接识别错误折叠蛋白的通用酶，而其他蛋白，如 ERp57 和 ERp72，则具有更专门的作用。在这里，我们报告了 ERp72（也称为 CaBP2 或 PDI A4）N 端部分的高分辨率 X 射线晶体结构，该结构包含两个 a(0)a 催化硫氧还蛋白样结构域。该结构表明，与其他硫氧还蛋白样结构域相比，a(0)结构域包含一个额外的 N 端β-链和β5-α4 环的不同构象。a 结构域的结构表明，一个保守的精氨酸残基插入疏水区并与催化位点附近的保守谷氨酸残基形成盐桥。全长 ERp72 的结构模型表明，所有三个催化位点大致相对，并且定位相邻的疏水区，这些区域可能参与蛋白质底物结合。
