The crystal structure of the carbohydrate-recognition domain of the glycoprotein sorting receptor p58/ERGIC-53 reveals an unpredicted metal-binding site and conformational changes associated with calcium ion binding

被引:45
作者
Velloso, LM
Svensson, K
Pettersson, RF
Lindqvist, Y [1 ]
机构
[1] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Ludwig Inst Canc Res, Stockholm Branch, S-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
calcium ion binding; crystallography; lectin; protein sorting; secretory pathway;
D O I
10.1016/j.jmb.2003.10.031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
p58/ERGIC-53 is a calcium-dependent animal lectin that acts as a cargo. receptor, binding to a set of glycoproteins in the endoplasmic reticulum (ER) and transporting them to the Golgi complex. It is similar in structure to calcium-dependent leguminous lectins. We have determined the structure of the carbohydrate-recognition domain of p58/ERGIC-53 in its calcium-bound form. The structure reveals localized but large conformational changes in relation to the previously determined metal ion-free 1 structure, mapping mostly to the ligand-binding site. It reveals the presence of two calcium ion-binding sites located 6 Angstrom apart, one of which has no equivalent in the plant lectins. The second metal ion-binding site present in that class of lectins, binding Mn2+, is absent from p58/ERGIC-53. The absence of a short loop in the ligand-binding site in this protein suggests that it has adapted to optimally bind the high-marmose Man(8)(GIcNAc)(2) glycan common to glycoproteins at the ER exit stage. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:845 / 851
页数:7
相关论文
共 37 条
  • [31] Lectin control of protein folding and sorting in the secretory pathway
    Schrag, JD
    Procopio, DO
    Cygler, M
    Thomas, DY
    Bergeron, JJM
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (01) : 49 - 57
  • [32] The structure of calnexin, an ER chaperone involved in quality control of protein folding
    Schrag, JD
    Bergeron, JJM
    Li, YG
    Borisova, S
    Hahn, M
    Thomas, DY
    Cygler, M
    [J]. MOLECULAR CELL, 2001, 8 (03) : 633 - 644
  • [33] SCHWEIZER A, 1993, J CELL SCI, V104, P671
  • [34] Expression, purification, refolding and crystallization of the carbohydrate-recognition domain of p58/ERGIC-53, an animal C-type lectin involved in export of glycoproteins from the endoplasmic reticulum
    Velloso, LM
    Svensson, K
    Lahtinen, U
    Schneider, G
    Pettersson, RF
    Lindqvist, Y
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 : 536 - 538
  • [35] Crystal structure of the carbohydrate recognition domain of p58/ERGIC-53, a protein involved in glycoprotein export from the endoplasmic reticulum
    Velloso, LM
    Svensson, K
    Schneider, G
    Pettersson, RF
    Lindqvist, Y
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (18) : 15979 - 15984
  • [36] ERGL, a novel gene related to ERGIC-53 that is highly expressed in normal and neoplastic prostate and several other tissues
    Yerushalmi, N
    Keppler-Hafkemeyer, A
    Vasmatzis, G
    Liu, XF
    Olsson, P
    Bera, TK
    Duray, P
    Lee, B
    Pastan, I
    [J]. GENE, 2001, 265 (1-2) : 55 - 60
  • [37] Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex
    Zhang, B
    Cunningham, MA
    Nichols, WC
    Bernat, JA
    Seligsohn, U
    Pipe, SW
    McVey, JH
    Schulte-Overberg, U
    de Bosch, NB
    Ruiz-Saez, A
    White, GC
    Tuddenham, EGD
    Kaufman, RJ
    Ginsburg, D
    [J]. NATURE GENETICS, 2003, 34 (02) : 220 - 225