Plasmodium falciparum merozoite surface protein 3: oligomerization, self-assembly, and heme complex formation

J Biol Chem. 2014 Feb 14;289(7):3856-68. doi: 10.1074/jbc.M113.520239. Epub 2013 Dec 19.


Merozoite surface protein 3 of Plasmodium falciparum, a 40-kDa protein that also binds heme, has been biophysically characterized for its tendency to form highly elongated oligomers. This study aims to systematically analyze the regions in MSP3 sequence involved in oligomerization and correlate its aggregation tendency with its high affinity for binding with heme. Through size exclusion chromatography, dynamic light scattering, and transmission electron microscopy, we have found that MSP3, previously known to form elongated oligomers, actually forms self-assembled filamentous structures that possess amyloid-like characteristics. By expressing different regions of MSP3, we observed that the previously described leucine zipper region at the C terminus of MSP3 may not be the only structural element responsible for oligomerization and that other peptide segments like MSP3(192-196) (YILGW) may also be required. MSP3 aggregates on incubation were transformed to long unbranched amyloid fibrils. Using immunostaining methods, we found that 5-15-μm-long fibrillar structures stained by anti-MSP3 antibodies were attached to the merozoite surface and also associated with erythrocyte membrane. We also found MSP3 to bind several molecules of heme by UV spectrophotometry, HPLC, and electrophoresis. This study suggested that its ability to bind heme is somehow related to its inherent characteristics to form oligomers. Moreover, heme interaction with a surface protein like MSP3, which does not participate in hemozoin formation, may suggest a protective role against the heme released from unprocessed hemoglobin released after schizont egress. These studies point to the other roles that MSP3 may play during the blood stages of the parasite, in addition to be an important vaccine candidate.

Keywords: Amyloid; Erythrocyte; Heme; Infectious Diseases; Malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / chemistry*
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / metabolism
  • Erythrocytes / chemistry
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology
  • Heme / chemistry*
  • Heme / genetics
  • Heme / metabolism
  • Hemeproteins / chemistry
  • Hemeproteins / genetics
  • Hemeproteins / metabolism
  • Humans
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / metabolism
  • Plasmodium falciparum / chemistry*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Protein Multimerization / physiology*
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Schizonts / chemistry
  • Schizonts / metabolism


  • Antigens, Protozoan
  • Hemeproteins
  • Protozoan Proteins
  • merozoite surface protein 3, Plasmodium
  • hemozoin
  • Heme