4GKY

Crystal structure of a carbohydrate-binding domain

4GKY の概要

• エントリーDOI: 10.2210/pdb4gky/pdb
• 関連するPDBエントリー: 3A4U 3LCP
• 分子名称: Protein ERGIC-53, CALCIUM ION, alpha-D-mannopyranose, ... (5 entities in total)
• 機能のキーワード: protein transport, endoplasmic reticulum
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29117.30

構造登録者

Page, R.C.,Zheng, C.,Nix, J.C.,Misra, S.,Zhang, B. (登録日: 2012-08-13, 公開日: 2013-06-05, 最終更新日: 2024-10-30)

主引用文献

Zheng, C.,Page, R.C.,Das, V.,Nix, J.C.,Wigren, E.,Misra, S.,Zhang, B.
Structural Characterization of Carbohydrate Binding by LMAN1 Protein Provides New Insight into the Endoplasmic Reticulum Export of Factors V (FV) and VIII (FVIII).
J.Biol.Chem., 288:20499-20509, 2013

PubMed Abstract: LMAN1 (ERGIC-53) is a key mammalian cargo receptor responsible for the export of a subset of glycoproteins from the endoplasmic reticulum. Together with its soluble coreceptor MCFD2, LMAN1 transports coagulation factors V (FV) and VIII (FVIII). Mutations in LMAN1 or MCFD2 cause the genetic bleeding disorder combined deficiency of FV and FVIII (F5F8D). The LMAN1 carbohydrate recognition domain (CRD) binds to both glycoprotein cargo and MCFD2 in a Ca(2+)-dependent manner. To understand the biochemical basis and regulation of LMAN1 binding to glycoprotein cargo, we solved crystal structures of the LMAN1-CRD bound to Man-α-1,2-Man, the terminal carbohydrate moiety of high mannose glycans. Our structural data, combined with mutagenesis and in vitro binding assays, define the central mannose-binding site on LMAN1 and pinpoint histidine 178 and glycines 251/252 as critical residues for FV/FVIII binding. We also show that mannobiose binding is relatively independent of pH in the range relevant for endoplasmic reticulum-to-Golgi traffic, but is sensitive to lowered Ca(2+) concentrations. The distinct LMAN1/MCFD2 interaction is maintained at these lowered Ca(2+) concentrations. Our results suggest that compartmental changes in Ca(2+) concentration regulate glycoprotein cargo binding and release from the LMAN1·MCFD2 complex in the early secretory pathway.

PubMed: 23709226
DOI: 10.1074/jbc.M113.461434

実験手法

X-RAY DIFFRACTION (2.4201 Å)