PF3D7_1362100

PF3D7_1362100 (14-3-3II) is a phosphorylation-dependent reader and scaffold protein in Plasmodium falciparum that couples phospho-signaling to distinct cellular compartments (PMID:23308157, PMID:21084299, PMID:27129434). In the context of chromatin, it binds parasite histone H3 and acts as a phospho-reader with preference for H3S28ph over H3S10ph, a selectivity consistent with conservation of the phosphopeptide-binding residues (PMID:23308157). It also engages the erythrocyte membrane-skeleton protein dematin after the latter is internalized by the parasite, an interaction that strictly requires dematin phosphorylation at Ser124 and Ser333, two canonical 14-3-3 binding motifs (PMID:21084299). In a PKA-signaling context, PF3D7_1362100 physically binds and colocalizes with the AKAP-like protein PfAKAL and additionally interacts with the PKA regulatory subunit PfPKA-R, positioning it to bridge PfAKAL to PfPKA-R; it is itself phosphorylated in vitro by PKA, indicating its scaffold interactions are subject to PKA-mediated regulation (PMID:27129434). Beyond these three phosphorylation-dependent binding activities, no further mechanistic detail—including in vivo functional consequences or a knockout phenotype—has been characterized in the available corpus.

1. 2010 Medium

   Established that PF3D7_1362100 can capture a host-derived substrate in a phospho-specific manner, defining it as a phosphorylation-dependent binding module rather than a constitutive interactor.

   Evidence Co-immunoprecipitation and in vitro binding of phosphorylated versus non-phosphorylated erythrocyte dematin

   PMID:21084299

   Open questions at the time

   • Functional consequence of the dematin interaction for the parasite is unknown
   • The kinase phosphorylating dematin Ser124/Ser333 in this context is not identified
   • Interaction shown in vitro; not validated in situ within the parasite
2. 2013 Medium

   Answered whether PF3D7_1362100 reads chromatin marks by showing it selectively binds phospho-histone H3, establishing a nuclear phospho-reader activity with defined mark preference.

   Evidence Recombinant pulldown with parasite histones plus an H3 phosphopeptide panel, supported by in silico structural conservation analysis

   PMID:23308157

   Open questions at the time

   • Downstream chromatin/transcriptional consequence of H3S28ph reading not defined
   • In vivo occupancy on parasite chromatin not demonstrated
   • The kinase generating H3S28ph is not identified
3. 2016 Medium

   Placed PF3D7_1362100 in the PKA signaling architecture by showing it bridges an AKAP-like protein to the PKA regulatory subunit and is itself a PKA substrate, implicating it as a scaffold whose interactions are regulated by phosphorylation.

   Evidence Reciprocal pulldowns with recombinant proteins and parasite extracts, immunofluorescence colocalization, and an in vitro radiolabel PKA kinase assay

   PMID:27129434

   Open questions at the time

   • The functional output of the PfAKAL–PF3D7_1362100–PfPKA-R bridge is not demonstrated in vivo
   • The residue(s) on PF3D7_1362100 phosphorylated by PKA are not mapped
   • Whether PKA phosphorylation enhances or disrupts specific interactions is untested

• Whether the three characterized activities—H3S28ph reading, dematin binding, and PKA-scaffolding—operate independently or as part of a unified regulatory program, and the in vivo phenotype of PF3D7_1362100 loss, remain unresolved.
• No genetic knockout or knockdown phenotype in the corpus
• No structural model of PF3D7_1362100 bound to any of its partners
• Temporal/stage regulation of the three binding activities not addressed