AMA1 (apical membrane antigen 1, PF3D7_1133400, UniProt Q7KQK5) notes

Automated deep research was unavailable in this environment (Falcon auth failure,
invalid OpenAI key). These notes are a manual literature review based on the UniProt
record, the cached publications cited in GOA, and one additional primary paper
(PMID:21788485) fetched for this review. No -deep-research-*.md file was created.

Identity and structure

• UniProt Q7KQK5 (TrEMBL, unreviewed; no gene symbol, ORF PF3D7_1133400), 622 aa,
  single-pass type I membrane protein of the apicomplexan AMA1 family.
• Many crystal structures of the ectodomain (residues ~97-442), e.g. PDB 1Z40, 3ZWZ
  (with a PfRON2 peptide), 3SRJ (with R1 peptide).
• Cloned in 1989 and named for its apparent apical localization
  PMID:2701947
  and transport to the merozoite surface
  PMID:2701947

Localization

• Microneme: unprocessed precursor resides in micronemes of schizonts
  PMID:12228305
  PMID:12228305
• Merozoite surface after prodomain removal
  PMID:12228305
• Moving/tight junction during invasion, with RON complex
  PMID:22737069
  No GO CC term exists for the moving junction (OLS search returned nothing).
• GOA membrane (IEA) is correct but too general; plasma membrane (merozoite surface)
  plus microneme is more informative.
• apical complex (TAS, 1989): true but general; micronemes are apical complex
  organelles and microneme is already annotated by IDA.

Molecular function: RON2 binding

• AMA1 binds directly to RON2, a rhoptry-neck protein that the parasite inserts into the
  host erythrocyte membrane
  PMID:22737069
  PMID:22737069
  PMID:22737069
• Binding of RON2 to the AMA1 hydrophobic pocket commits the merozoite to invasion
  PMID:21788485
• PfAMA1 coimmunoprecipitates with PfRON4 (likely indirect, via the RON2/RON4/RON5
  complex)
  PMID:16835460
• Because RON2 sits in the host membrane, AMA1-RON2 binding is effectively binding to a
  component exposed on the host cell surface, supporting host cell surface binding.
  However, RON2 is a parasite protein, so host cell surface receptor binding
  (GO:0046789; a host receptor) would be inaccurate.

Biological process: erythrocyte invasion

• Conditional DiCre knockdown in P. falciparum
  PMID:24571085
  PMID:24571085
• Dissenting genetic data (P. berghei and Toxoplasma knockouts): AMA1 is an adhesin that
  helps attachment but is dispensable for penetration
  PMID:24108241
  PMID:24108241
  Note: the full text of PMID:24108241 uses P. berghei and T. gondii mutants; I found no
  P. falciparum experiment, so the IDA host cell surface binding on PfAMA1 is a
  cross-species inference from a knockout adhesion phenotype. The function is still
  plausible for PfAMA1 via RON2 binding and is supported by the P. falciparum
  structural work, so it is accepted as the core molecular function.
  Yap et al. discuss that residual AMA1 or compensation (e.g., by the paralog-like
  AMA1 homologues/MAEBL in the KO lines) may explain the discrepancy
  PMID:24571085
• GO term symbiont entry into host (GO:0044409) is appropriately parasite-side (the
  merozoite enters the host erythrocyte) but is less specific than the evidence supports.
  The child "symbiont entry into host cell" (GO:0046718) is defined around breaching the
  membrane and releasing the symbiont or its genome into the cytoplasm, which does not fit
  apicomplexan invasion. Its own descendant GO:0085017 "entry into host cell by a
  symbiont-containing vacuole" does: OLS gives its definition as invasion forming "a
  vacuole in which the symbiont resides", beginning with attachment to a host membrane
  that invaginates and ending when that membrane closes behind the new vacuole -- the
  moving junction AMA1 anchors, and the cited phenotype is precisely a failure to seal the
  parasitophorous vacuole. GOA already uses GO:0085017 for P. falciparum MSP1 (IDA) and
  CSP (IMP), so the GO:0044409 row is MODIFYed to GO:0085017 for accuracy and for
  consistency with the rest of the invasion machinery.
• adhesion of symbiont to host cell (GO:0044650) is supported by the Bargieri KO
  adhesion phenotypes in P. berghei/T. gondii but not tested directly in P. falciparum;
  not proposed as NEW (conservative).

Decisions summary

Also proposed a new cellular component term for the apicomplexan moving (tight)
junction, since OLS returned no GO term for it and it is the structure in which AMA1
actually acts.