Structure and function of Class I α1,2-mannosidases involved in glycoprotein synthesis and endoplasmic reticulum quality control

Native disulphide bonds are essential for the structure and function of many membrane and secretory proteins. Disulphide bonds are formed, reduced and isomerized in the endoplasmic reticulum of mammalian cells by a family of oxidoreductases, which includes protein disulphide isomerase (PDI), ERp57, ERp72, P5 and PDIR. This review will discuss how these enzymes are maintained in either an oxidized redox state that allows them to form disulphide bonds in substrate proteins or a reduced form that allows them to perform isomerization and reduction reactions, how these opposing pathways may co-exist within the same compartment and why so many oxidoreductases exist when PDI alone can perform all three of these functions.

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Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I molecules

Immunological Reviews ◽

10.1111/j.1600-065x.1997.tb00949.x ◽

1997 ◽

Vol 155 (1) ◽

pp. 165-174 ◽

Cited By ~ 97

Author(s):

Miguel Lopez-Botet ◽

Juan J. Perez-Villar ◽

Marta Carretero ◽

Antonio Rodriguez ◽

Ignacio Melero ◽

...

Keyword(s):

Hla Class I ◽

Structure And Function ◽

Class I ◽

Receptor Complex ◽

Lectin Receptor ◽

Hla Class I Molecules ◽

And Function

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Endoplasmic reticulum quality control and congenital pathology

Journal of Applied Biomedicine ◽

10.32725/jab.2005.021 ◽

2005 ◽

Vol 3 (4) ◽

pp. 159-165

Author(s):

Marek Michalak

Keyword(s):

Quality Control ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Quality Control

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Mechanism of Class 1 (Glycosylhydrolase Family 47) α-Mannosidases Involved inN-Glycan Processing and Endoplasmic Reticulum Quality Control

Journal of Biological Chemistry ◽

10.1074/jbc.m500119200 ◽

2005 ◽

Vol 280 (16) ◽

pp. 16197-16207 ◽

Cited By ~ 89

Author(s):

Khanita Karaveg ◽

Aloysius Siriwardena ◽

Wolfram Tempel ◽

Zhi-Jie Liu ◽

John Glushka ◽

...

Keyword(s):

Quality Control ◽

Endoplasmic Reticulum ◽

Bond Cleavage ◽

Substrate Analog ◽

Acid And Base ◽

Class 1 ◽

Glycoside Bond ◽

Endoplasmic Reticulum Quality Control ◽

Mutant Forms ◽

Hydrolytic Mechanism

Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming ofN-glycans attached to misfolded glycoproteins by ER α-mannosidase I and subsequent recognition by the ER degradation-enhancing α-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER α-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel3S1sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the1C4conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the –1 subsite. A novel3H4conformation is proposed as the exploded transition state.

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