MLEC

Malectin (MLEC) is an endoplasmic reticulum glycoprotein quality control factor that supports the biogenesis of nascent glycoproteins through its association with the Oligosaccharyltransferase (OST) complex (PMID:38895409). During coronavirus infection it is co-opted to promote viral glycoprotein production and genome replication: knockdown of MLEC reduces infectious titers of murine hepatitis virus and impairs SARS-CoV-2 replication, while viral nsp2 engages MLEC-associated proteins and the MLEC interactome is remodeled yet retains its OST association (PMID:38895409). Beyond this quality-control role, MLEC has been linked to immune regulation, where it promotes M1-to-M2 macrophage polarization (PMID:28972276). The molecular basis of the macrophage polarization activity has not been characterized in the available corpus.

1. 2018 Low

   Established a candidate immune-regulatory role for MLEC by tying expression-lowering polymorphisms to a defined cellular phenotype, raising the question of how an ER quality-control factor influences immune cell behavior.

   Evidence SNP genotyping with in vitro macrophage polarization and expression assays in macrophage cell lines

   PMID:28972276

   Open questions at the time

   • Single in vitro functional assay with limited mechanistic detail; not independently confirmed
   • No molecular pathway linking MLEC to polarization defined
   • No connection to its ER glycoprotein quality-control function established
2. 2025 Medium

   Defined MLEC's molecular activity as ER glycoprotein quality control acting through the OST complex and showed this function is exploited during coronavirus infection to support viral glycoprotein biogenesis and replication.

   Evidence Quantitative proteomics, siRNA knockdown with infectious-titer readout, and interactome/co-IP analysis in coronavirus-infected cells (preprint)

   PMID:38895409

   Open questions at the time

   • Not yet peer-reviewed
   • Specific glycoprotein substrates handled by MLEC during infection not identified
   • Mechanism by which nsp2 reshapes the MLEC interactome unresolved

• How MLEC's ER glycoprotein quality-control activity mechanistically connects to its reported role in macrophage polarization remains unknown.
• No unifying mechanism linking glycoprotein handling to immune cell phenotype
• Substrate repertoire of MLEC in either context undefined