Multiple charged amino acids of Plasmodium falciparum SURFIN4.1 N-terminal region are important for efficient export to the red blood cell

Ben-Yeddy Abel Chitama; Shinya Miyazaki; Xiaotong Zhu; Wataru Kagaya; Kazuhide Yahata; Osamu Kaneko

doi:10.1016/j.parint.2019.04.019

Multiple charged amino acids of Plasmodium falciparum SURFIN_4.1 N-terminal region are important for efficient export to the red blood cell

Parasitol Int. 2019 Aug:71:186-193. doi: 10.1016/j.parint.2019.04.019. Epub 2019 Apr 24.

Authors

Ben-Yeddy Abel Chitama¹, Shinya Miyazaki², Xiaotong Zhu³, Wataru Kagaya⁴, Kazuhide Yahata⁵, Osamu Kaneko⁶

Affiliations

¹ Leading Program, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: benchitama@gmail.com.
² Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Leiden Malaria Research Group, Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. Electronic address: shinya841212@gmail.com.
³ Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China. Electronic address: xtzhu@cmu.edu.cn.
⁴ Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Environmental Parasitology, Graduate School of Tokyo Medical and Dental University, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-0034, Japan; Department of Parasitology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan. Electronic address: wataru.kagaya@gmail.com.
⁵ Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: kyahata@nagasaki-u.ac.jp.
⁶ Leading Program, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: okaneko@nagasaki-u.ac.jp.

PMID: 31028841
DOI: 10.1016/j.parint.2019.04.019

Abstract

Plasmodium falciparum, an obligate intracellular protozoan parasite which causes the severe form of human malaria, exports numerous proteins to the infected red blood cell that are important for its survival and of severe pathological effect to its host. These proteins and their export mechanisms are candidates for drug and vaccine development, and among them is the Plasmodium SURFIN family of proteins. Previously we showed that the N-terminal region along with the sequence surrounding the transmembrane domain of SURFIN_4.1 is essential for its export to Maurer's clefts in the red blood cell cytoplasm. We proposed that this region is recognized by a machinery responsible for protein translocation across the parasitophorous vacuole membrane surrounding the parasite. To understand the export mechanism further, we utilized a fluorescent protein-tagged mini-SURFIN_4.1 consisting of the minimum essential components for export. Alanine scanning of all charged amino acids within the N-terminal region revealed that replacement of 3 glutamic acid and 2 lysine residues significantly impairs the export efficiency of this protein across the parasitophorous vacuole membrane. In addition, N-terminally Myc-tagged mini-SURFIN_4.1 and mini-SURFIN_4.2 with similar architectures were detected with anti-Myc antibody at Maurer's clefts, indicating that elements required for export to Maurer's clefts are conserved between SURFIN_4.1 and SURFIN_4.2, and that N-terminal sequences of these SURFIN members are not cleaved during export. Our results implicate a conserved nature of SURFIN export to the red blood cell, particularly an important role of multiple glutamic acid and lysine residues in the SURFIN N-terminal region.

Keywords: Erythrocyte; Malaria; Plasmodium falciparum; Protein export; SURFIN.

MeSH terms

Amino Acids / chemistry*
Erythrocytes / parasitology*
Glutamic Acid / chemistry
Host-Parasite Interactions*
Humans
Lysine / chemistry
Membrane Proteins / chemistry*
Plasmodium falciparum / genetics*
Protein Transport
Protozoan Proteins / chemistry*

Substances

Amino Acids
Membrane Proteins
Protozoan Proteins
SURFIN4.1 protein, Plasmodium falciparum
Glutamic Acid
Lysine