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Papers by Manjiri Kulkarni

Research paper thumbnail of Crystal structures of dengue virus protein revealed ED3 sero-specificity

Acta Crystallographica Section A Foundations and Advances, 2017

Research paper thumbnail of Modelling and experimental assessment of a buried Leu-Ile mutation in Dengue envelope domain III

Biochemical and Biophysical Research Communications, 2016

Research paper thumbnail of Crystal structure of DEN4 ED3 mutant with epitope two residues substituted from DEN3 ED3

Research paper thumbnail of Crystallographic studies of sero-specific dengue ED3 immune response

Acta Crystallographica Section A Foundations and Advances, 2017

Research paper thumbnail of Folding of the Ig-Like Domain of the Dengue Virus Envelope Protein Analyzed by High-Hydrostatic-Pressure NMR at a Residue-Level Resolution

Biomolecules

Dengue fever is a mosquito-borne endemic disease in tropical and subtropical regions, causing a s... more Dengue fever is a mosquito-borne endemic disease in tropical and subtropical regions, causing a significant public health problem in Southeast Asia. Domain III (ED3) of the viral envelope protein contains the two dominant putative epitopes and part of the heparin sulfate receptor binding region that drives the dengue virus (DENV)’s fusion with the host cell. Here, we used high-hydrostatic-pressure nuclear magnetic resonance (HHP-NMR) to obtain residue-specific information on the folding process of domain III from serotype 4 dengue virus (DEN4-ED3), which adopts the classical three-dimensional (3D) ß-sandwich structure known as the Ig-like fold. Interestingly, the folding pathway of DEN4-ED3 shares similarities with that of the Titin I27 module, which also adopts an Ig-like fold, but is functionally unrelated to ED3. For both proteins, the unfolding process starts by the disruption of the N- and C-terminal strands on one edge of the ß-sandwich, yielding a folding intermediate stable ...

Research paper thumbnail of Systematic mutational analysis of epitope-grafted ED3’s immunogenicity reveals a DENV3-DENV4 bi-serospecific ED3 mutant

Dengue viruses are classified into four serotypes (DENV1∼4), and the severe forms of dengue disea... more Dengue viruses are classified into four serotypes (DENV1∼4), and the severe forms of dengue disease, the dengue hemorrhagic fever and shock syndrome, are caused by sero-cross-reacting antibodies. However, the residue determinants of the serospecificity and sero-cross-reactivity are yet to be identified. Here, we report an epitope grafting mutational analysis of the serospecificity and cross-serospecificity of the envelope protein domain 3 (ED3; 107 residues, ∼11.6kDa), which contains two major putative epitopes of DENVs. To this end, we constructed ED3 from DENV3 (3ED3) and DENV4 (4ED3), and six epitope-grafted variants, where we transferred epitope 1 (L304I, K305D, V309M, and S310A) and/or epitope 2 (D383N, K384S, K387T, and N389H) of 4ED3 onto 3ED3 and vice versa. Mice immunization using 3ED3 and 4ED3 generated serotype-specific antisera, as expected. Similarly, most epitope-grafted ED3s produced antisera serospecific to the template ED3 with little or no cross-recognition of ED3 ...

Research paper thumbnail of Biophysical studies and high resolution crystal structure of dengue envelope protein domain III (ED3)

Research paper thumbnail of Structural and biophysical analysis of sero-specific immune responses using epitope grafted Dengue ED3 mutants

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2015

Research paper thumbnail of Crystal structure of DEN4 ED3 mutant with L387I

Research paper thumbnail of Crystal structures of dengue virus protein revealed ED3 sero-specificity

Acta Crystallographica Section A Foundations and Advances, 2017

Research paper thumbnail of Modelling and experimental assessment of a buried Leu-Ile mutation in Dengue envelope domain III

Biochemical and Biophysical Research Communications, 2016

Research paper thumbnail of Crystal structure of DEN4 ED3 mutant with epitope two residues substituted from DEN3 ED3

Research paper thumbnail of Crystallographic studies of sero-specific dengue ED3 immune response

Acta Crystallographica Section A Foundations and Advances, 2017

Research paper thumbnail of Folding of the Ig-Like Domain of the Dengue Virus Envelope Protein Analyzed by High-Hydrostatic-Pressure NMR at a Residue-Level Resolution

Biomolecules

Dengue fever is a mosquito-borne endemic disease in tropical and subtropical regions, causing a s... more Dengue fever is a mosquito-borne endemic disease in tropical and subtropical regions, causing a significant public health problem in Southeast Asia. Domain III (ED3) of the viral envelope protein contains the two dominant putative epitopes and part of the heparin sulfate receptor binding region that drives the dengue virus (DENV)’s fusion with the host cell. Here, we used high-hydrostatic-pressure nuclear magnetic resonance (HHP-NMR) to obtain residue-specific information on the folding process of domain III from serotype 4 dengue virus (DEN4-ED3), which adopts the classical three-dimensional (3D) ß-sandwich structure known as the Ig-like fold. Interestingly, the folding pathway of DEN4-ED3 shares similarities with that of the Titin I27 module, which also adopts an Ig-like fold, but is functionally unrelated to ED3. For both proteins, the unfolding process starts by the disruption of the N- and C-terminal strands on one edge of the ß-sandwich, yielding a folding intermediate stable ...

Research paper thumbnail of Systematic mutational analysis of epitope-grafted ED3’s immunogenicity reveals a DENV3-DENV4 bi-serospecific ED3 mutant

Dengue viruses are classified into four serotypes (DENV1∼4), and the severe forms of dengue disea... more Dengue viruses are classified into four serotypes (DENV1∼4), and the severe forms of dengue disease, the dengue hemorrhagic fever and shock syndrome, are caused by sero-cross-reacting antibodies. However, the residue determinants of the serospecificity and sero-cross-reactivity are yet to be identified. Here, we report an epitope grafting mutational analysis of the serospecificity and cross-serospecificity of the envelope protein domain 3 (ED3; 107 residues, ∼11.6kDa), which contains two major putative epitopes of DENVs. To this end, we constructed ED3 from DENV3 (3ED3) and DENV4 (4ED3), and six epitope-grafted variants, where we transferred epitope 1 (L304I, K305D, V309M, and S310A) and/or epitope 2 (D383N, K384S, K387T, and N389H) of 4ED3 onto 3ED3 and vice versa. Mice immunization using 3ED3 and 4ED3 generated serotype-specific antisera, as expected. Similarly, most epitope-grafted ED3s produced antisera serospecific to the template ED3 with little or no cross-recognition of ED3 ...

Research paper thumbnail of Biophysical studies and high resolution crystal structure of dengue envelope protein domain III (ED3)

Research paper thumbnail of Structural and biophysical analysis of sero-specific immune responses using epitope grafted Dengue ED3 mutants

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2015

Research paper thumbnail of Crystal structure of DEN4 ED3 mutant with L387I