3O0W

Structural basis of carbohydrate recognition by calreticulin

3O0W の概要

• エントリーDOI: 10.2210/pdb3o0w/pdb
• 関連するPDBエントリー: 3O0V 3O0X
• 分子名称: Calreticulin, alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: jelly roll fold, chaperone, carbohydrate binding; calcium binding
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32006.71

構造登録者

Kozlov, G.,Gehring, K. (登録日: 2010-07-20, 公開日: 2010-09-29, 最終更新日: 2024-11-20)

主引用文献

Kozlov, G.,Pocanschi, C.L.,Rosenauer, A.,Bastos-Aristizabal, S.,Gorelik, A.,Williams, D.B.,Gehring, K.
Structural basis of carbohydrate recognition by calreticulin.
J.Biol.Chem., 285:38612-38620, 2010

PubMed Abstract: The calnexin cycle is a process by which glycosylated proteins are subjected to folding cycles in the endoplasmic reticulum lumen via binding to the membrane protein calnexin (CNX) or to its soluble homolog calreticulin (CRT). CNX and CRT specifically recognize monoglucosylated Glc(1)Man(9)GlcNAc(2) glycans, but the structural determinants underlying this specificity are unknown. Here, we report a 1.95-Å crystal structure of the CRT lectin domain in complex with the tetrasaccharide α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-Man. The tetrasaccharide binds to a long channel on CRT formed by a concave β-sheet. All four sugar moieties are engaged in the protein binding via an extensive network of hydrogen bonds and hydrophobic contacts. The structure explains the requirement for glucose at the nonreducing end of the carbohydrate; the oxygen O(2) of glucose perfectly fits to a pocket formed by CRT side chains while forming direct hydrogen bonds with the carbonyl of Gly(124) and the side chain of Lys(111). The structure also explains a requirement for the Cys(105)-Cys(137) disulfide bond in CRT/CNX for efficient carbohydrate binding. The Cys(105)-Cys(137) disulfide bond is involved in intimate contacts with the third and fourth sugar moieties of the Glc(1)Man(3) tetrasaccharide. Finally, the structure rationalizes previous mutagenesis of CRT and lays a structural groundwork for future studies of the role of CNX/CRT in diverse biological pathways.

PubMed: 20880849
DOI: 10.1074/jbc.M110.168294

実験手法

X-RAY DIFFRACTION (1.95 Å)