User:Susan Corradino

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*Susan Corradino

• Graduate student
• State University of New York, Old Westbury
• Old Westbury, NY, USA
• Education (Biology). B.S. Marine Vertebrate Biology.

• User:Susan Corradino/Sandbox1 calnexin

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Calnexin: Not Just Another Chaperone Protein

IntroductionIntroduction

Calnexin is an integral protein found in the plasma membrane of the endoplasmic reticulum. This protein functions as a chaperone protein , forming a super-complex which aids in the formation of the MHC complex. The MHC complex comes in two forms, MHC class I and MHC class II. This molecule is responsible for peptide presentation to T cells in the adaptive immune response. MHC I complex forms and matures in the endoplasmic reticulum of the cell. Once the peptide is bound to the heavy chain of the peptide binding cleft, the molecule will migrate out of the endoplasmic reticulum to the cytosol eventually making its way to the cell surface for presentation to T lymphocytes. T cells will bind to the MHC I complex when antigen recognition has occurred . Without calnexin, the MHC complex would be compromised and ultimately be unable to present the peptide required for the immune response.

3D Structure3D Structure

This molecule is asymmetrical in shape with two unique domains. The long protruding arm of the protein is thought to function with the communication between calnexin and other proteins, specifically ERp57, a secondary chaperon protein in the formation of the MHC I complex, this section of the protein gives it a unique crystal structure that is unlike other proteins . This arm also provides the contact point for all intermolecular communication . There are two significant disulfide bonds found in the long arm of calnexin, - and - . Important amino acids in this section of the crystal structure of calnexin include and residues of found in the lectin domain as well as and residues . This aspect of the crystal structure will allow the arm of the molecule to wrap around associate proteins to form the super complex for the MHC I . The second domain which is globular lectin in nature provides the ability to monovalently bind glycan. The unique arm of this molecule is the result of a specialized region called the P domain. This region contains four copies of proline-rich linear sequences. The binding region on the body of the molecule is located at and . This region will allow the P domain to enclose the respective monomer.

FunctionFunction

Calnexin is a chaperone protein that aids in the folding of the MHC I complex. Research shows that calnexin assists in the folding of the heavy chains of the molecule . Research shows in mice, D. melanogaster, and humans, that when calnexin was experimentally removed, the heavy chains were unable to fold properly resulting in the misfolding and inhibition of complex formation .

Calnexin has an additional function when paired with glucosidases, the molecule will help to regulate the folding of glycoproteins. The protein ensures that misfolded glycoproteins remain in the ER until they are disposed of by the appropriate regulating structures. Calnexin has also been described as a player in aiding in the proper folding of polypeptides. In the absence of calnexin glycans will fold as a drastically lower rate .

Calnexin has been conservered through out evolution as it is a molecule found in most eukaryotic cells. One can conclude that role of calnexin in the adaptive immune response is critical to survival and thus evolved in the common ancestor. Through phylogenetic analysis it was determined that calnexin has been preserved in angiosperms, which date back to around 420 million years ago .

2D Image2D Image

ConclusionConclusion

Calnexin is a critical chaperone protein found in the plasma membrane of the endoplasmic reticulum. The protein has been conserved throughout evolutionary history due to its important function. Without calnexin the MHC I complex would be unable to present peptides to lymphocytes. Calnexin's unique structure provides an additional focus point and proves to provide a location for attachment to external proteins during the formation of the MHC complex. Without calnexin, the adaptive immune response would be irrevocably compromised.