YihA3

YihA3 (PF3D7_0812220) is a nuclear-encoded GTPase of Plasmodium falciparum implicated in ribosomal large subunit (LSU) biogenesis in the apicoplast (PMID:32057832). It localizes to both the apicoplast and the cytosol (PMID:32057832) and functions as an active GTPase in vitro as a recombinant protein (PMID:32057832). YihA3 binds the ribosomal large subunit — associating with surrogate E. coli LSU in a nucleotide-independent manner in vitro and co-immunoprecipitating with parasite organellar and/or cytosolic LSU in vivo — consistent with a role in late-stage LSU assembly (PMID:32057832). Beyond this dual-organelle localization, GTPase activity, and LSU association, no further mechanistic detail for PF3D7_0812220 has been characterized in the available corpus.

1. 2020 Medium

   Establishing where YihA3 acts was the first step in assigning it a cellular role; the finding that it resides in both the apicoplast and cytosol placed it at the interface of organellar and cytosolic machinery.

   Evidence Subcellular fractionation and immunofluorescence with specific antibodies in P. falciparum

   PMID:32057832

   Open questions at the time

   • Relative abundance and functional contribution in each compartment not quantified
   • Trafficking mechanism to the apicoplast not defined
2. 2020 Medium

   Demonstrating intrinsic GTP hydrolysis confirmed YihA3 is a bona fide active GTPase rather than a degenerate nucleotide-binding protein, providing the enzymatic basis for its proposed regulatory role.

   Evidence In vitro GTPase activity assay with recombinant protein

   PMID:32057832

   Open questions at the time

   • GTPase activation partners or GAP/GEF regulators not identified
   • Kinetic parameters and effect of ribosome binding on hydrolysis not resolved
   • Single lab, single method
3. 2020 Medium

   Linking YihA3 to the ribosome addressed what it acts upon; nucleotide-independent binding to the large subunit in vitro plus in vivo co-IP with parasite LSU implicated it in late-stage LSU assembly.

   Evidence Pulldown with surrogate E. coli ribosomes and reciprocal co-immunoprecipitation with specific antibodies from P. falciparum lysate

   PMID:32057832

   Open questions at the time

   • Whether the in vivo interaction is with apicoplast, cytosolic, or both LSU populations not distinguished
   • Direct role in assembly not demonstrated by depletion or functional readout
   • Surrogate E. coli ribosome used in place of native apicoplast ribosome

• Whether YihA3 is essential and what specific step of LSU maturation its GTP hydrolysis regulates remain unresolved.
• No genetic knockout/knockdown phenotype reported
• No structural model of the YihA3–ribosome complex
• Coupling between GTP hydrolysis cycle and LSU assembly steps undefined