MSP7

MSRP2 (PF3D7_1334800) is a secreted member of the P. falciparum MSP7-related protein (MSRP) family that acts in the asexual blood stage in association with the MSP-1 complex rather than as a surface-resident merozoite protein (PMID:20472690, PMID:12477792). It binds the amino-terminal region of MSP-1, an interaction first captured through the P. yoelii homologue and confirmed biochemically for P. falciparum MSRP2 (PMID:12477792). During schizont maturation MSRP2 undergoes sequential proteolytic cleavage—it is a substrate of the subtilisin-like protease PfSUB1—generating 28- and 25-kDa forms, and the soluble 25-kDa form is released into the culture supernatant upon merozoite egress rather than remaining on the merozoite surface (PMID:20472690, PMID:21220481). MSRP2 is also exported into the host erythrocyte as a PEXEL/HT-negative exported protein (PNEP), placing it in a translocation pathway independent of the classical PEXEL export signal (PMID:23950716). Despite these interactions and processing events, targeted disruption of msrp2 in P. falciparum 3D7 produces no detectable growth or invasion phenotype in vitro, so its precise cellular function during blood-stage development is not established in the available corpus (PMID:20472690). In the rodent parasite P. berghei, the ortholog PbMSRP2 binds host P-selectin, hinting at a possible host-interaction role, but the P. berghei ortholog is also dispensable for life-cycle progression (PMID:26045295, PMID:26222913).

1. 2002 Medium

   Establishing a binding partner was the first step in placing MSRP2 in a functional context; the question was whether it associates with any known merozoite protein.

   Evidence Yeast two-hybrid screen with P. yoelii MSP-1 N-terminus as bait plus in vitro binding assay with P. falciparum MSRP2

   PMID:12477792

   Open questions at the time

   • Binding region on MSRP2 not mapped
   • Functional consequence of the MSRP2–MSP-1 interaction not defined
   • Interaction not confirmed in vivo in the parasite
2. 2004 Medium

   The localization and fate of MSRP2 was addressed in the rodent homologue, testing whether it behaves as a surface protein of the MSP-1/MSP-7 complex.

   Evidence Immunofluorescence and immunoprecipitation from lysate and supernatant of P. yoelii schizonts

   PMID:14742548

   Open questions at the time

   • Shown in P. yoelii, not P. falciparum
   • Mechanism of release not defined
   • Does not establish a role for the released protein
3. 2010 Medium

   The processing and secretory fate of P. falciparum MSRP2, and its functional requirement, were directly tested to determine whether it is a surface merozoite protein essential for growth.

   Evidence Immunoblot with anti-MSRP2 antibodies, subcellular fractionation, and targeted gene disruption with growth/invasion assays in P. falciparum 3D7

   PMID:20472690

   Open questions at the time

   • No detectable knockout phenotype leaves function unexplained
   • Redundancy with other MSRP members not tested
   • Identity of the proteases generating the 28/25-kDa forms not resolved here
4. 2011 Medium

   The protease responsible for MSRP2 maturation was identified, linking its cleavage to the egress protease cascade.

   Evidence Mass spectrometry of the late blood-stage proteome combined with bioinformatic prediction of PfSUB1 cleavage sites

   PMID:21220481

   Open questions at the time

   • No in vitro cleavage reconstitution with purified PfSUB1
   • Functional consequence of cleavage unknown
   • Cleavage site positions not experimentally verified
5. 2013 Medium

   The trafficking of MSRP2 beyond the parasite was addressed, asking whether it reaches the host cell and by what route.

   Evidence Fluorescent reporter fusion assays and live imaging identifying MSRP family members as PEXEL/HT-negative exported proteins in P. falciparum

   PMID:23950716

   Open questions at the time

   • Export shown at family level; MSRP2-specific export signal not mapped
   • Function of exported MSRP2 in the erythrocyte unknown
   • Translocation machinery not identified
6. 2015 Low

   A candidate host-directed activity was tested by asking whether the MSRP2 ortholog engages a host receptor.

   Evidence Extracellular protein interaction screen with biochemical binding and Sialyl-Lewis(X) competition assay showing PbMSRP2 binds mouse P-selectin

   PMID:26045295

   Open questions at the time

   • MSRP2-specific contribution reported alongside MSRP1
   • Shown in P. berghei, not P. falciparum
   • In vivo immune-modulatory consequence not demonstrated
7. 2015 Low

   The requirement of the MSRP2 ortholog across the full life cycle was tested to determine whether family redundancy masks an essential role.

   Evidence Triple gene deletion (msp7/mspr1/mspr2) in P. berghei with life-cycle progression assay

   PMID:26222913

   Open questions at the time

   • MSRP2 contribution cannot be isolated in the triple mutant
   • Shown in P. berghei rodent model
   • No phenotype leaves function undefined

• The core function of MSRP2 remains undefined: it binds MSP-1, is PfSUB1-processed, secreted and exported, yet no loss-of-function phenotype has been assigned in either P. falciparum or P. berghei.
• No causal role for MSRP2 in invasion, egress, or host modulation established
• Functional redundancy among MSRP members untested at the level of MSRP2-specific complementation
• P-selectin engagement not tested for P. falciparum MSRP2