4YS4

Crystal structure of Pf41 tandem 6-cys domains from Plasmodium falciparum

4YS4 の概要

• エントリーDOI: 10.2210/pdb4ys4/pdb
• 分子名称: Merozoite surface protein P41, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: antigens, immune system
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41683.04

構造登録者

Parker, M.L.,Peng, F.,Boulanger, M.J. (登録日: 2015-03-16, 公開日: 2015-10-14, 最終更新日: 2025-04-02)

主引用文献

Parker, M.L.,Peng, F.,Boulanger, M.J.
The Structure of Plasmodium falciparum Blood-Stage 6-Cys Protein Pf41 Reveals an Unexpected Intra-Domain Insertion Required for Pf12 Coordination.
Plos One, 10:e0139407-e0139407, 2015

PubMed Abstract: Plasmodium falciparum is an apicomplexan parasite and the etiological agent of severe human malaria. The complex P. falciparum life cycle is supported by a diverse repertoire of surface proteins including the family of 6-Cys s48/45 antigens. Of these, Pf41 is localized to the surface of the blood-stage merozoite through its interaction with the glycophosphatidylinositol-anchored Pf12. Our recent structural characterization of Pf12 revealed two juxtaposed 6-Cys domains (D1 and D2). Pf41, however, contains an additional segment of 120 residues predicted to form a large spacer separating its two 6-Cys domains. To gain insight into the assembly mechanism and overall architecture of the Pf12-Pf41 complex, we first determined the 2.45 Å resolution crystal structure of Pf41 using zinc single-wavelength anomalous dispersion. Structural analysis revealed an unexpected domain organization where the Pf41 6-Cys domains are, in fact, intimately associated and the additional residues instead map predominately to an inserted domain-like region (ID) located between two β-strands in D1. Notably, the ID is largely proteolyzed in the final structure suggesting inherent flexibility. To assess the contribution of the ID to complex formation, we engineered a form of Pf41 where the ID was replaced by a short glycine-serine linker and showed by isothermal titration calorimetry that binding to Pf12 was abrogated. Finally, protease protection assays showed that the proteolytic susceptibility of the ID was significantly reduced in the complex, consistent with the Pf41 ID directly engaging Pf12. Collectively, these data establish the architectural organization of Pf41 and define an essential role for the Pf41 ID in promoting assembly of the Pf12-Pf41 heterodimeric complex.

PubMed: 26414347
DOI: 10.1371/journal.pone.0139407

実験手法

X-RAY DIFFRACTION (2.45 Å)