BIOMAT Database Logo BIOMAT Database Logo

An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A. 2022

Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Center for Infectious Disease Research, Seattle, Washington, USA.

Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target. In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L). Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface. The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA.

UI MeSH Term Description Entries
D008288 Malaria A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia. Marsh Fever,Plasmodium Infections,Remittent Fever,Infections, Plasmodium,Paludism,Fever, Marsh,Fever, Remittent,Infection, Plasmodium,Plasmodium Infection
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002809 Chondroitin Sulfates Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate. Chondroitin 4-Sulfate,Chondroitin 6-Sulfate,Chondroitin Sulfate A,Chondroitin Sulfate C,Blutal,Chondroitin 4-Sulfate, Aluminum Salt,Chondroitin 4-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Potassium Salt,Chondroitin 6-Sulfate, Sodium Salt,Chondroitin Sulfate,Chondroitin Sulfate 4-Sulfate, Sodium Salt,Chondroitin Sulfate, Calcium Salt,Chondroitin Sulfate, Iron (+3) Salt,Chondroitin Sulfate, Iron Salt,Chondroitin Sulfate, Potassium Salt,Chondroitin Sulfate, Sodium Salt,Chondroitin Sulfate, Zinc Salt,Chonsurid,Sodium Chondroitin Sulfate,Translagen,Chondroitin 4 Sulfate,Chondroitin 4 Sulfate, Aluminum Salt,Chondroitin 4 Sulfate, Potassium Salt,Chondroitin 6 Sulfate,Chondroitin 6 Sulfate, Potassium Salt,Chondroitin 6 Sulfate, Sodium Salt,Chondroitin Sulfate 4 Sulfate, Sodium Salt,Chondroitin Sulfate, Sodium,Sulfate, Chondroitin,Sulfate, Sodium Chondroitin,Sulfates, Chondroitin
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000913 Antibodies, Protozoan Immunoglobulins produced in a response to PROTOZOAN ANTIGENS. Protozoan Antibodies
D000953 Antigens, Protozoan Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered. Protozoan Antigens

Related Publications

Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium falciparum-infected erythrocytes are associated with transcription of var2csa.
May 2005, Infection and immunity,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Adherence of Plasmodium falciparum-infected erythrocytes to chondroitin 4-sulfate.
August 1999, Bioscience reports,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Characteristics of Plasmodium falciparum-infected-erythrocyte adhesion to chondroitin sulfate.
June 2008, Infection and immunity,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria.
July 2012, The Journal of biological chemistry,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Plasmodium falciparum: Assessment of parasite-infected red blood cell binding to placental chondroitin proteoglycan and bovine tracheal chondroitin sulfate A.
October 2009, Experimental parasitology,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum.
August 2006, Molecular and biochemical parasitology,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Overproduction, purification and crystallization of a chondroitin sulfate A-binding DBL domain from a Plasmodium falciparum var2csa-encoded PfEMP1 protein.
March 2008, Acta crystallographica. Section F, Structural biology and crystallization communications,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
The NTS-DBL2X region of VAR2CSA induces cross-reactive antibodies that inhibit adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A.
October 2011, The Journal of infectious diseases,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.
October 2023, Nature communications,
Gladys J Keitany, and Bethany J Jenkins, and Harold T Obiakor, and Shaji Daniel, and Atis Muehlenbachs, and Jean-Philippe Semblat, and Benoit Gamain, and Justin Y A Doritchamou, and Sanjay A Desai, and Nicholas J MacDonald, and David L Narum, and Robert Morrison, and Tracy Saveria, and Marissa Vignali, and Andrew V Oleinikov, and Michal Fried, and Patrick E Duffy
VAR2CSA Ectodomain Labeling in Plasmodium falciparum Infected Red Blood Cells and Analysis via Flow Cytometry.
August 2023, Bio-protocol,
Copied contents to your clipboard!