Importance of glycosidases in mammalian glycoprotein biosynthesis

Herscovics, Annetté

doi:10.1016/s0304-4165(99)00171-3

“…Following the translocation of nascent proteins into the endoplasmic reticulum (ER), the Glc 3 Man 9 GlcNAc 2 oligosaccharide is transferred to asparagine residues and sequentially processed by ER α-glucosidases, which remove the three glucose residues and by α-mannosidases that trim at least one mannose residue (Kornfeld & Kornfeld 1985, Herscovics 1999a.Alpha-mannosidases are grouped within families 38 and 47 of the glycosyl hydrolase classification (Henrissat 1991, Henrissat & Davies 1997. Members of family 38 are less specific than enzymes from family 47, removing α1,2, α1,3 and α1,6-linked mannose units (Daniel et al 1994, Herscovics 1999a.…”

mentioning

confidence: 99%

“…Following the translocation of nascent proteins into the endoplasmic reticulum (ER), the Glc 3 Man 9 GlcNAc 2 oligosaccharide is transferred to asparagine residues and sequentially processed by ER α-glucosidases, which remove the three glucose residues and by α-mannosidases that trim at least one mannose residue (Kornfeld & Kornfeld 1985, Herscovics 1999a.…”

mentioning

confidence: 99%

Purification and biochemica characterisation of endoplasmic reticulum α 1,2-mannosidase from Sporothrix schenckiil

Mora-Montes

¹

,

Robledo-Ortiz

²

,

Gonzalez-Sanchez

³

et al. 2010

Mem. Inst. Oswaldo Cruz

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N-glycosylation of proteins is a common post-translational modification in eukaryotic cells. Following the translocation of nascent proteins into the endoplasmic reticulum (ER), the Glc 3 Man 9 GlcNAc 2 oligosaccharide is transferred to asparagine residues and sequentially processed by ER α-glucosidases, which remove the three glucose residues and by α-mannosidases that trim at least one mannose residue (Kornfeld & Kornfeld 1985, Herscovics 1999a.Alpha-mannosidases are grouped within families 38 and 47 of the glycosyl hydrolase classification (Henrissat 1991, Henrissat & Davies 1997. Members of family 38 are less specific than enzymes from family 47, removing α1,2, α1,3 and α1,6-linked mannose units (Daniel et al. 1994, Herscovics 1999a. Enzymes from family 47 are α1,2-mannosidases that participate in the trimming of N-glycans and in ER-associated degradation (Herscovics 1999a, b, 2001, Helenius & Aebi 2004. Two subgroups of enzymes comprise family 47: the ER α1,2-mannosidases that trim only one mannose residue from Man 9 GlcNAc 2 (M 9 ) generating Man 8 GlcNAc isomer B (M 8 B) (Ziegler & Trimble 1991, Tremblay & Herscovics 1999, Mora-Montes et al. 2004, Movsichoff et al. 2005; and Golgi α1,2-mannosidases from mammalian cells and filamentous fungi, which act after the ER enzyme to remove three α1,2-linked mannose units, generating Man 5 GlcNAc 2 , an intermediate required for the biosynthesis of complex and hybrid N-glycans (Yoshida et al. 1993, Lal et al. 1998, Ichishima et al. 1999, Eades & Hintz 2000, Tremblay & Herscovics 2000, Lobsanov et al. 2002, Akao et al. 2006. Lower eukaryotes, such as Saccharomyces cerevisiae, lack Golgi α1,2-mannosidases and synthesise only high-mannose N-glycans (Herscovics 1999b).Sporothrix schenckii, the etiological agent of sporotrichosis, is a dimorphic fungus that grows as filamentous and yeast cells during saprophytic and parasitic phases, respectively. This organism is closely related to Ophiostoma stenoceras, a non-pathogenic fungus that grows on sapwood from coniferous and hardwood trees (de Beer et al. 2003). Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of colonised materials (soil, wood, decomposed vegetable matter) or inhalation of the conidia (Ramos-e-Silva et al. 2007). The disease has been reported as an emerging mycosis in HIV-infected humans (Durden & Elewski 1997). The cell wall of S. schenckii is being actively researched, as this structure has an important role in adhesion to host tissues and is the main source of antigens that can be exploited in the immuno-diagnosis of the disease (LopesBezerra et al. 2006). The cell wall of S. schenckii contains β1,3, β1,6 and β1,4-glucans (Lopes-Bezerra et al. In order to gain insight into the processing steps of Nglycan biosynthesis, a membrane-bound α-mannosidase from S. schenckii was targeted for purification and characterisation. Biochemical characterisation and intracellular localisation studies indicated that this enzyme is an ER α1,2-mannosidase and therefore a new member of glycosyl hydrol...

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“…Protein N-glycosylation plays important roles in immunity [1] and a-mannosidase is one type of the key enzymes in N-glycosylation [2][3][4][5]. Although many have been known on the molecular nature and function of these enzymes, the biological significance of a-mannosidases is still not completely understood.…”

Section: Discussionmentioning

confidence: 99%

“…a-Mannosidase is one type of the key enzymes in catalyzing N-glycosylation, which catalyzes the hydrolysis of terminal non-reducing a-D-mannose residues in a-d-mannosides and is involved in the trimming reaction during N-glycan maturation [2][3][4]. a-Mannosidase has multiple forms [5].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

Li

¹

,

Ju

²

,

Chen

³

et al. 2006

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Protein: Cotranslational and Posttranslational Modification in Organelles

Shandala

¹

,

Parkinson-Lawrence

²

,

Brooks

³

2011

Encyclopedia of Life Sciences

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Polypeptides can be modified in the rough endoplasmic reticulum (RER) either during their synthesis (cotranslational) or after the initial synthesis has been completed (posttranslational). These structural modifications are also referred to as protein processing events, which can include N ‐linked glycosylation; O ‐linked glycosylation; glycolipid attachment; disulfide bond formation to generate secondary structure; modification to fold the polypeptide into a stable tertiary structure (low free energy state) and proteolytic processing of the nascent polypeptide or precursor protein to generate either protein subunits or mature functional protein. Cotranslational and posttranslational modification is therefore critical for generating stable protein structure and ultimately appropriate function. Protein processing is also used to generate appropriate targeting signals, which, following synthesis, are used to traffic each protein to either its correct subcellular compartment or extracellular destination. Key Concepts: Transcribed mRNA contains the code for polypeptide synthesis, which is exported from the nucleus to the cytoplasm to initiate protein translation. For noncytosolic proteins, the mature mRNA is bound by ribosomes in the cytoplasm, to synthesise a signal sequence, and this complex is then transported to the RER for additional polypeptide synthesis. Newly synthesised polypeptides undergo cotranslational modification in the RER. N ‐linked glycosylation is an essential structural component that is added to the nascent polypeptide in the RER and is involved in the initial steps of protein folding. Molecular chaperones in the RER facilitate protein folding to generate correct protein secondary and tertiary structure. There is a quality control process to ensure that only correctly folded and processed proteins exit the RER. Posttranslational modifications can take place in different cellular organelles such as the RER, Golgi, endosomes, lysosomes and secretory vesicles. The Golgi is involved in posttranslational glycoprocessing and the generation of signals for targeting protein to its final destination. Posttranslational proteolytic processing can be used to generate protein subunits and mature functional proteins.

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Importance of glycosidases in mammalian glycoprotein biosynthesis

Cited by 259 publications

References 77 publications

Purification and biochemica characterisation of endoplasmic reticulum α 1,2-mannosidase from Sporothrix schenckiil

Purification and biochemica characterisation of endoplasmic reticulum α 1,2-mannosidase from Sporothrix schenckiil

Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

Protein: Cotranslational and Posttranslational Modification in Organelles

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