BDP2

BDP2 (PF3D7_1212900) is a nuclear bromodomain protein of Plasmodium falciparum that functions as a constitutive partner of PfBDP1 within a chromatin-associated bromodomain protein complex (PMID:23181666, PMID:26067602, PMID:35493110). It was first placed in the nucleus by organellar proteomics with transgenic validation (PMID:23181666), and subsequently shown to physically associate with PfBDP1 in interaction proteomics, defining a core BDP1/BDP2 module (PMID:26067602). This complex is recruited to chromatin in an acetylation-level-dependent manner, as demonstrated by acetylated histone peptide pull-downs coupled to quantitative interaction proteomics, linking BDP2 to acetylation-marked chromatin and the regulation of invasion-related genes (PMID:26067602, PMID:31728527). BDP2 is also a member of a larger BDP1/BDP2/BDP7 assembly associated with variant surface antigen gene silencing, but the direct functional experiments (conditional knockdown, ChIP-seq) in that context were performed on PfBDP1 and PfBDP7 rather than on BDP2 itself (PMID:35493110). Beyond its membership in these complexes and its acetylation-dependent chromatin recruitment, no BDP2-specific loss-of-function phenotype has been characterized in the available corpus.

1. 2012 Medium

   Establishing where BDP2 acts was the first question; localizing it to the nucleus positioned it as a candidate chromatin-associated factor rather than a cytoplasmic protein.

   Evidence High-accuracy mass spectrometry of nuclear proteome fractions with transgenic cell line validation in P. falciparum

   PMID:23181666

   Open questions at the time

   • Localization alone does not define a molecular activity or binding partners
   • No chromatin-binding specificity established at this stage
2. 2015 Medium

   Whether BDP2 works alone or within a complex was resolved by showing it physically associates with PfBDP1, placing BDP2 in a bromodomain protein complex tied to invasion gene regulation.

   Evidence Co-immunoprecipitation / interaction proteomics via BDP1 pulldown identifying BDP2 in P. falciparum

   PMID:26067602

   Open questions at the time

   • Single Co-IP without reciprocal BDP2 pulldown reported
   • Direct contribution of BDP2 to invasion gene regulation not tested
   • Stoichiometry and interaction interface unknown
3. 2019 Medium

   How the BDP1/BDP2 complex finds chromatin was addressed by demonstrating acetylation-level-dependent recruitment, connecting BDP2 to acetylated histone marks.

   Evidence Acetylated histone peptide pull-downs plus quantitative interaction proteomics and tagging in P. falciparum

   PMID:31728527

   Open questions at the time

   • Which specific acetyl marks BDP2's own bromodomain reads was not resolved separately from BDP1
   • Direct DNA/chromatin binding by BDP2 not distinguished from complex-level recruitment
4. 2022 Low

   The composition of the complex was extended to include PfBDP7 and linked to variant surface antigen silencing, but BDP2's specific role remained inferred from membership rather than tested directly.

   Evidence Interaction proteomics confirming BDP2 in the BDP1/BDP2/BDP7 complex, with ChIP-seq and conditional knockdown performed on BDP1 and BDP7 in P. falciparum

   PMID:35493110

   Open questions at the time

   • No conditional knockdown or knockout of BDP2 itself performed; its function is inferred from complex membership
   • Whether BDP2 is required for VSA silencing is untested
   • BDP2's contribution distinct from BDP1/BDP7 is undefined

• The direct functional role of BDP2 remains unresolved: no BDP2-specific loss-of-function phenotype, target gene set, or bromodomain acetyl-mark specificity has been established independent of its complex partners.
• BDP2 knockdown/knockout phenotype unknown
• BDP2 bromodomain ligand specificity uncharacterized
• Contribution of BDP2 to invasion gene versus VSA gene regulation undetermined