Lectin control of protein folding and sorting in the secretory pathway.
Glycan moieties are essential for folding, sorting and targeting of glycoproteins through the secretory pathway to various cellular compartments. The molecular mechanisms that underlie these processes, however, are only now coming to light. Recent crystallographic and NMR studies of proteins located in the endoplasmic reticulum (ER), Golgi complex and ER-Golgi intermediate compartment have illuminated their roles in glycoprotein folding and secretion. Calnexin and calreticulin, both ER-resident proteins, have lectin domains that are crucial for their function as chaperones. The crystal structure of the carbohydrate-recognition domain of ER-Golgi intermediate compartment (ERGIC)-53 complements the biochemical and functional characterization of the protein, confirming that a lectin domain is essential for the role of this protein in sorting and transfer of glycoproteins from the ER to the Golgi complex. The lectin domains of calnexin and ERGIC-53 are structurally similar, although there is little primary sequence similarity. By contrast, sequence similarity between ERGIC-53 and vesicular integral membrane protein (VIP36), a Golgi-resident protein, leaves little doubt that a similar lectin domain is central to the transport and/or sorting functions of VIP36. The theme emerging from these studies is that carbohydrate recognition and modification are central to mediation of glycoprotein folding and secretion.
Schrag
Joseph D
JD
Biotechnology Research Institute, NRC of Canada, Montreal, PQ, Canada.
Procopio
Daniela O
DO
Cygler
Miroslaw
M
Thomas
David Y
DY
Bergeron
John J M
JJ
D000595:Amino Acid Sequence; D000818:Animals; D037281:Calnexin / Q000737:chemistry / Q000502:physiology; D037282:Calreticulin / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D037102:Lectins / Q000502:physiology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
D037282:Calreticulin; D037102:Lectins; D037281:Calnexin