Structural basis of carbohydrate recognition by calreticulin

Area of Science:

• Molecular Biology
• Structural Biology
• Glycobiology

Background:

• The calnexin cycle facilitates protein folding within the endoplasmic reticulum.
• Calnexin (CNX) and calreticulin (CRT) are key chaperones recognizing specific glycans on proteins.
• The structural basis for CNX/CRT specificity towards monoglucosylated glycans remains unclear.

Purpose of the Study:

• To elucidate the structural determinants of calreticulin's (CRT) specificity for monoglucosylated glycans.
• To provide a molecular understanding of CRT's interaction with its carbohydrate ligand.

Main Methods:

• X-ray crystallography was employed to determine the structure of the CRT lectin domain.
• The structure was solved at 1.95-Å resolution in complex with a specific tetrasaccharide.

Main Results:

• A detailed structure of the CRT lectin domain bound to a tetrasaccharide (α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-Man) was obtained.
• The binding involves extensive hydrogen bonds and hydrophobic interactions within a concave β-sheet channel.
• The structure explains the necessity of terminal glucose and the Cys(105)-Cys(137) disulfide bond for efficient glycan binding.

Conclusions:

• The crystal structure provides a molecular basis for CRT's recognition of monoglucosylated glycans.
• This finding clarifies the role of specific structural features in CRT/CNX function.
• The study lays the foundation for further research into the calnexin cycle's involvement in biological pathways.