Interaction of Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 with Band 3 on Human Erythrocyte Surface Facilitates Parasite Growth

Alam, Mohd Shoeb; Choudhary, Vandana; Zeeshan, Mohammad; Tyagi, Rupesh Kumar; Rathore, Sumit; Sharma, Yagya D.

doi:10.1074/jbc.m115.644906

Cited by 36 publications

(64 citation statements)

References 40 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Basigin Interacts with PvTRAg38 through its P 2 RegionPvTRAg38 interacts with erythrocytes through two peptide regions, P 2 and P 4 at amino acid positions 161-178 and 197-214, respectively (19). Further studies revealed that last six amino acids of this P 4 peptide were not involved in erythrocyte binding, but multiple residues of the remaining 12 amino acid peptides interact with its erythrocyte receptor (20).…”

Section: Resultsmentioning

confidence: 99%

“…Among these three erythrocyte proteins, band 3 has already been confirmed as one of the erythrocyte receptors for this parasite ligand (19). Therefore, we planned to study direct interaction between PvTRAg38 and each of the other two erythrocyte proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, the chymotrypsin-sensitive human erythrocyte receptor for this parasite protein was identified as band 3 (19). Therefore, in pursuit of identifying the second erythrocyte receptor for PvTRAg38, we used a more sensitive method of LC-MS/MS-based multidimensional protein identification technology (MudPIT) 4 analysis (21,22).…”

Section: Resultsmentioning

confidence: 99%

“…Among these two erythrocyte receptors, one was sensitive to chymotrypsin and interacts through the P 4 region and the other receptor was resistant to this enzyme. The chymotrypsin-sensitive erythrocyte receptor for the P 4 region has recently been identified as band 3 (19). Furthermore, multiple residues of the P 4 region interact with three different ectodomains of band 3 (20).…”

mentioning

confidence: 99%

“…Recently, we have reported that several P. vivax tryptophan-rich antigens (PvTRAgs) belonging to the pv-fam-a family were highly immunogenic in humans, have conserved sequences in parasite population, and bind to host erythrocytes through two receptors (14 -17). One of the pv-fam-a family proteins called PvTRAg38, which is expressed at merozoite stage (18), is also highly immunogenic (17), binds to host erythrocytes (14), and promotes the parasite growth in the heterologous P. falciparum culture system (19). We have been able to define two erythrocyte-binding regions, P 2 (at amino acid position 167-178) and P 4 (at amino acid position 198 -208), of this parasite ligand that interact with two different erythrocyte receptors.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth

Rathore

Dass

Kandari

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Luke O'NeillElucidating the molecular mechanisms of the host-parasite interaction during red cell invasion by Plasmodium is important for developing newer antimalarial therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich antigen PvTRAg38, which is expressed by its merozoites, binds to host erythrocytes, and interferes with parasite growth. Interaction of this parasite ligand with the host erythrocyte occurs through its two regions present at amino acid positions 167-178 (P 2 ) and 197-208 (P 4 ). Each region recognizes its own erythrocyte receptor. Previously, we identified band 3 as the chymotrypsin-sensitive erythrocyte receptor for the P 4 region, but the other receptor, binding to P 2 region, remained unknown. Here, we have identified basigin as the second erythrocyte receptor for PvTRAg38, which is resistant to chymotrypsin. The specificity of interaction between PvTRAg38 and basigin was confirmed by direct interaction where basigin was specifically recognized by P 2 and not by the P 4 region of this parasite ligand. Interaction between P 2 and basigin is stabilized through multiple amino acid residues, but Gly-171 and Leu-175 of P 2 were more critical. These two amino acids were also critical for parasite growth. Synthetic peptides P 2 and P 4 of PvTRAg38 interfered with the parasite growth independently but had an additive effect if combined together indicating involvement of both the receptors during red cell invasion. In conclusion, PvTRAg38 binds to two erythrocyte receptors basigin and band 3 through P 2 and P 4 regions, respectively, to facilitate parasite growth. This advancement in our knowledge on molecular mechanisms of host-parasite interaction can be exploited to develop therapeutics against P. vivax malaria.Plasmodium vivax causes malaria in a huge human population in Southeast Asia and South America, thus affecting their socio-economic conditions. Although this parasite causes benign malaria, it can also cause complications, similar to Plasmodium falciparum, leading to death (1, 2). Because of the limited success to cultivate this parasite in the laboratory and very low parasitemia in P. vivax patients, the biology of this parasite is not explored in as much detail as that of P. falciparum. Not only is the parasite becoming more virulent, it is also showing resistance toward commonly used anti-malarial drugs. Furthermore, there is no vaccine available against this parasite. For effective control of this disease, newer anti-malarial drugs and vaccines need to be developed. Thus, identification of drug and vaccine targets is urgently needed. In this regard, the parasite molecules expressed at the merozoite stage and involved in erythrocyte invasion hold their significance as they have been proven to be the most effective drug or vaccine targets (3).Large numbers of host and parasite molecules need to interact with each other during erythrocyte invasion by the malarial parasite. Identification of all the host erythrocyte receptors and their respective parasi...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth

Rathore

Dass

Kandari

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

et al. 2016

Self Cite

View full text Add to dashboard Cite

Tryptophan-rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan-rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor-ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197-208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria.

show abstract

Multiple Plasmodium vivax proteins of Pv-fam-a family interact with human erythrocyte receptor Band 3 and have a role in red cell invasion

Alam

Zeeshan

Rathore

et al. 2016

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Interaction of Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 with Band 3 on Human Erythrocyte Surface Facilitates Parasite Growth

Cited by 36 publications

References 40 publications

Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth

Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

Multiple Plasmodium vivax proteins of Pv-fam-a family interact with human erythrocyte receptor Band 3 and have a role in red cell invasion

Contact Info

Product

Resources

About