The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. / Meno, Kåre; Thorsted, Peter B; Ipsen, Henrik; Kristensen, Ole; Larsen, Jørgen; Spangfort, Michael D; Gajhede, Michael; Lund, Kaare.

In: Journal of Immunology, Vol. 175, No. 6, 2005, p. 3835-45.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Meno, K, Thorsted, PB, Ipsen, H, Kristensen, O, Larsen, J, Spangfort, MD, Gajhede, M & Lund, K 2005, 'The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen', Journal of Immunology, vol. 175, no. 6, pp. 3835-45.

APA

Meno, K., Thorsted, P. B., Ipsen, H., Kristensen, O., Larsen, J., Spangfort, M. D., ... Lund, K. (2005). The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. Journal of Immunology, 175(6), 3835-45.

Vancouver

Meno K, Thorsted PB, Ipsen H, Kristensen O, Larsen J, Spangfort MD et al. The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. Journal of Immunology. 2005;175(6):3835-45.

Author

Meno, Kåre ; Thorsted, Peter B ; Ipsen, Henrik ; Kristensen, Ole ; Larsen, Jørgen ; Spangfort, Michael D ; Gajhede, Michael ; Lund, Kaare. / The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. In: Journal of Immunology. 2005 ; Vol. 175, No. 6. pp. 3835-45.

Bibtex

@article{3654d7d4bbce48a5963db55422cb54ba,
title = "The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen",
abstract = "Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced. The sequence of the proDer p 1 allergen was modified to reduce glycosylation and to abolish enzymatic activity. The resulting rproDer p 1 preparation was homogenous and stable and yielded crystals diffracting to a resolution of 1.61 A. The active site is located in a large cleft on the surface of the molecule. The 80-aa pro-peptide adopts a unique fold that interacts with the active site cleft and a substantial adjacent area on the mature region, excluding access to the cleft and the active site. Studies performed using crossed-line immunoelectrophoresis and IgE inhibition experiments indicated that several epitopes are covered by the pro-peptide and that the epitopes on the recombinant mature molecule are indistinguishable from those on the natural one. The structure confirms previous results suggesting a preference for aliphatic residues in the important P2 position in substrates. Sequence variations in related species are concentrated on the surface, which explains the existence of cross-reacting and species-specific antibodies. This study describes the first crystal structure of one of the clinically most important house dust mite allergens, the cysteine protease Der p 1.",
keywords = "Allergens, Animals, Arthropod Proteins, Binding Sites, Cross Reactions, Crystallography, X-Ray, Epitopes, Genetic Engineering, Models, Molecular, Molecular Structure, Protein Conformation, Protein Precursors, Pyroglyphidae, Recombinant Proteins, Species Specificity, Substrate Specificity",
author = "K{\aa}re Meno and Thorsted, {Peter B} and Henrik Ipsen and Ole Kristensen and J{\o}rgen Larsen and Spangfort, {Michael D} and Michael Gajhede and Kaare Lund",
year = "2005",
language = "English",
volume = "175",
pages = "3835--45",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

RIS

TY - JOUR

T1 - The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen

AU - Meno, Kåre

AU - Thorsted, Peter B

AU - Ipsen, Henrik

AU - Kristensen, Ole

AU - Larsen, Jørgen

AU - Spangfort, Michael D

AU - Gajhede, Michael

AU - Lund, Kaare

PY - 2005

Y1 - 2005

N2 - Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced. The sequence of the proDer p 1 allergen was modified to reduce glycosylation and to abolish enzymatic activity. The resulting rproDer p 1 preparation was homogenous and stable and yielded crystals diffracting to a resolution of 1.61 A. The active site is located in a large cleft on the surface of the molecule. The 80-aa pro-peptide adopts a unique fold that interacts with the active site cleft and a substantial adjacent area on the mature region, excluding access to the cleft and the active site. Studies performed using crossed-line immunoelectrophoresis and IgE inhibition experiments indicated that several epitopes are covered by the pro-peptide and that the epitopes on the recombinant mature molecule are indistinguishable from those on the natural one. The structure confirms previous results suggesting a preference for aliphatic residues in the important P2 position in substrates. Sequence variations in related species are concentrated on the surface, which explains the existence of cross-reacting and species-specific antibodies. This study describes the first crystal structure of one of the clinically most important house dust mite allergens, the cysteine protease Der p 1.

AB - Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced. The sequence of the proDer p 1 allergen was modified to reduce glycosylation and to abolish enzymatic activity. The resulting rproDer p 1 preparation was homogenous and stable and yielded crystals diffracting to a resolution of 1.61 A. The active site is located in a large cleft on the surface of the molecule. The 80-aa pro-peptide adopts a unique fold that interacts with the active site cleft and a substantial adjacent area on the mature region, excluding access to the cleft and the active site. Studies performed using crossed-line immunoelectrophoresis and IgE inhibition experiments indicated that several epitopes are covered by the pro-peptide and that the epitopes on the recombinant mature molecule are indistinguishable from those on the natural one. The structure confirms previous results suggesting a preference for aliphatic residues in the important P2 position in substrates. Sequence variations in related species are concentrated on the surface, which explains the existence of cross-reacting and species-specific antibodies. This study describes the first crystal structure of one of the clinically most important house dust mite allergens, the cysteine protease Der p 1.

KW - Allergens

KW - Animals

KW - Arthropod Proteins

KW - Binding Sites

KW - Cross Reactions

KW - Crystallography, X-Ray

KW - Epitopes

KW - Genetic Engineering

KW - Models, Molecular

KW - Molecular Structure

KW - Protein Conformation

KW - Protein Precursors

KW - Pyroglyphidae

KW - Recombinant Proteins

KW - Species Specificity

KW - Substrate Specificity

M3 - Journal article

C2 - 16148130

VL - 175

SP - 3835

EP - 3845

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -

ID: 40318507