Erythrocytic Stage-dependent Regulation of Oligomerization of Plasmodium Ribosomal Protein P2

Abstract

Background: Plasmodium falciparum P2 (PfP2) protein plays nonribosomal roles through SDS-and DTT-resistant oligomerization. Results: For SDS-and DTT-sensitive oligomerization, the 53rd cysteine of PfP2 plays an important role. Conclusion: DTT-and SDS-resistant oligomerization of PfP2 was propagated by differentially expressed parasite proteins. Significance: Analysis of regulation of PfP2 oligomerization in parasite-infected erythrocytes may help in understanding the export of P2 to erythrocyte surface.

Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function

“…However, intrinsically disordered proteins have been shown to be resistant to SDS-PAGE denaturation. Several of them may remain in a non-covalently bond state with other proteins upon SDS treatment and to run as complexes on SDS-PAGE (Tramentozzi et al, 2008 ; Shimada and Kitada, 2011 ; Das et al, 2012 ; Falson et al, 2015 ; Sadler et al, 2015 ). Furthermore, hydrophilic residues of disordered proteins and hybrid proteins containing ordered and disordered regions, such as the Xenopus XPA (Xeroderma pigmentosum group A) and the prostate-associated gene 4 protein, may bind SDS poorly, which allows them to migrate noticeably slower than the migration expected on the basis of their AA sequence (Iakoucheva et al, 2001 ; Tompa, 2002 ; Receveur-Bréchot et al, 2006 ; Zeng et al, 2011 ; Uversky and Dunker, 2012 ).…”

Translational regulation during stage transitions in malaria parasites

“…P0 has been found to also have surface expression on merozoites, and antibodies against P0 inhibit erythrocyte invasion in both P. falciparum and Plasmodium yoelii . Additionally, PfP2 is exported to the surface of infected erythrocytes for 6–8 h during early schizogony, starting at 26–28 h after merozoite invasion . The surface‐exposed PfP2 is present mostly as SDS‐resistant homotetramers, and export is concomitant with extensive oligomerization of the protein.…”

In vivo formation of Plasmodium falciparum ribosomal stalk — A unique mode of assembly without stable heterodimeric intermediates

“…From this respect the unusual mode of stalk assembling, with no stable heterodimers, might have important biological consequences, facilitating physiologically relevant P2 oligomer's formation. P2 oligomers occur in a developmentally dependent fashion, exhibiting oligomerization at the trophozoite stages in the erythrocytic development cycle; the P2 gets exported to the infected erythrocyte surface at 30 h post-merozoite invasion, concomitant with extensive oligomerization [29,49]. This molecular behavior of the P2 protein does not fall into the generally accepted notion about the behavior of P-proteins, raising questions about the molecular background for such peculiarity.…”

“…The molecular behavior of P. falciparum proteins resembles the properties of P-proteins from other species, where individual P-proteins are present in various oligomeric forms in vitro [37,40,47]. Recently, a P2 homo-oligomer was found as a biologically relevant species in P. falciparum [48,49], suggesting that it may represent one of the functional forms of P2 in some stages of parasite development. Although the parasite individual P-proteins in general reflect the behavior of stalk proteins from other classes of organisms, the reconstruction of the P1-P2 or uL10/P0-P1-P2 complexes using a previously developed in vitro denaturation/renaturation procedure for the P-proteins was found to be unsuccessful.…”