Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen

Mandar T. Naik; Chi Fon Chang; I. Chun Kuo; Camy C.H. Kung; Fong Cheng Yi; Kaw Yan Chua; Tai Huang Huang

doi:10.1016/j.str.2007.10.022

Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen

Mandar T. Naik, Chi Fon Chang, I. Chun Kuo, Camy C.H. Kung, Fong Cheng Yi, Kaw Yan Chua^*, Tai Huang Huang

^*Corresponding author for this work

Department of Physics

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long α helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab′ of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.

Original language	English
Pages (from-to)	125-136
Number of pages	12
Journal	Structure
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.str.2007.10.022
Publication status	Published - 2008 Jan 8

Keywords

MOLIMMUNO
PROTEINS

ASJC Scopus subject areas

Structural Biology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.str.2007.10.022

Cite this

@article{ba312a025f914b14b9ba6342940199bc,

title = "Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen",

abstract = "Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long α helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab′ of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.",

keywords = "MOLIMMUNO, PROTEINS",

author = "Naik, {Mandar T.} and Chang, {Chi Fon} and Kuo, {I. Chun} and Kung, {Camy C.H.} and Yi, {Fong Cheng} and Chua, {Kaw Yan} and Huang, {Tai Huang}",

note = "Funding Information: This work is supported, in part, by Academia Sinica and by grants NSC 95-2311-B-001-066-MY3 and NSC-95-2113-M-001-035-MY3 (T.-H.H.) from the National Science Council of the Republic of China. The NMR spectra were obtained at the High-Field Nuclear Magnetic Resonance Center, Taiwan, which is supported by the National Research Program for Genomic Medicine, the Republic of China. The software made available by Prof. Arthur Palmer (Columbia University, New York) is gratefully acknowledged. The Blo t 5-positive sera were gifted by the late Professor Kue-Hsiung Hsieh (National Taiwan University Hospital, Taipei). We thank Ellen Yu, Pei-Ju Fang, Wen-Jin Wu, and Hongmei Wen for technical assistance. This work is partly supported by a research grant (BMRC 03/1/21/18/217) from the Biomedical Research Council, Republic of Singapore to K.-Y.C. ",

year = "2008",

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doi = "10.1016/j.str.2007.10.022",

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AU - Naik, Mandar T.

AU - Chang, Chi Fon

AU - Kuo, I. Chun

AU - Kung, Camy C.H.

AU - Yi, Fong Cheng

AU - Chua, Kaw Yan

AU - Huang, Tai Huang

N1 - Funding Information: This work is supported, in part, by Academia Sinica and by grants NSC 95-2311-B-001-066-MY3 and NSC-95-2113-M-001-035-MY3 (T.-H.H.) from the National Science Council of the Republic of China. The NMR spectra were obtained at the High-Field Nuclear Magnetic Resonance Center, Taiwan, which is supported by the National Research Program for Genomic Medicine, the Republic of China. The software made available by Prof. Arthur Palmer (Columbia University, New York) is gratefully acknowledged. The Blo t 5-positive sera were gifted by the late Professor Kue-Hsiung Hsieh (National Taiwan University Hospital, Taipei). We thank Ellen Yu, Pei-Ju Fang, Wen-Jin Wu, and Hongmei Wen for technical assistance. This work is partly supported by a research grant (BMRC 03/1/21/18/217) from the Biomedical Research Council, Republic of Singapore to K.-Y.C.

PY - 2008/1/8

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N2 - Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long α helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab′ of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.

AB - Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long α helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab′ of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.

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ER -

Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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NMR solution structure of Blo t 5, a major mite allergen from Blomia tropicalis

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Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

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NMR solution structure of Blo t 5, a major mite allergen from Blomia tropicalis

Cite this