MCM6

In P. falciparum, MCM6 (PF3D7_1355100) is a physical interactor and phosphorylation substrate of the malarial cyclin-dependent kinase Pfmrk, linking it to CDK-regulated nuclear processes; substrate specificity for this phosphorylation is conferred by PfMAT1 within the Pfmrk kinase complex (PMID:20332005). Beyond this kinase–substrate relationship (PMID:20332005), no further mechanistic detail about MCM6's own catalytic activity, structural role, or DNA replication licensing function has been characterized in the available corpus.

1. 2010 Medium

   It was unknown which parasite proteins are targeted by the malarial CDK Pfmrk; identifying MCM6 as both a physical partner and a phosphorylation substrate established a direct link between this kinase and MCM6, and showed PfMAT1 confers specificity for MCM6 phosphorylation.

   Evidence Bacterial two-hybrid screen of a P. falciparum cDNA library plus in vitro/cell-based phosphorylation assay

   PMID:20332005

   Open questions at the time

   • The phosphorylation site(s) on MCM6 and the functional consequence of phosphorylation were not defined
   • MCM6's own catalytic or structural role in DNA replication was not demonstrated
   • Interaction rests on a single lab with limited orthogonal validation of MCM6 specifically

• Whether MCM6 functions in P. falciparum DNA replication licensing, its assembly into an MCM complex, and the physiological role of its Pfmrk-mediated phosphorylation remain unresolved.
• No demonstration of MCM6 helicase or replication-licensing activity in this organism
• No structural model or complex composition established for MCM6
• Functional impact of Pfmrk/PfMAT1-mediated phosphorylation on MCM6 not tested