1qmr

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1qmr, resolution 2.15Å

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BIRCH POLLEN ALLERGEN BET V 1 MUTANT N28T, K32Q, E45S, P108G

Overview

Human type 1 immediate allergic response symptoms are caused by mediator, release from basophils and mast cells. This event is triggered by, allergens aggregating preformed IgE Abs bound to the high-affinity, receptor (FcepsilonRI) on these cells. Thus, the allergen/IgE interaction, is crucial for the cascade leading to the allergic and anaphylactic, response. Two genetically engineered forms of the white birch pollen major, allergen Bet v 1 with point mutations directed at molecular surfaces have, been characterized. Four and nine point mutations led to a significant, reduction of the binding to human serum IgE, suggesting a mutation-induced, distortion of IgE-binding B cell epitopes. In addition, the mutated, allergens showed a decrease in anaphylactic potential, because histamine, release from human basophils was significantly reduced. Retained, alpha-carbon backbone folding pattern of the mutated allergens was, indicated by x-ray diffraction analysis and circular dichroism, spectroscopy. The rBet v 1 mutants were able to induce proliferation of T, cell lines derived from birch pollen allergic patients. The stimulation, indices were similar to the indices of nonmutated rBet v 1 and natural Bet, v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant, specific mouse IgG serum to block binding of human serum IgE to rBet v 1, demonstrates that the engineered rBet v 1 mutants are able to induce Abs, reactive with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine, candidates with improved efficacy/safety profiles for safer allergy, vaccination.

About this Structure

1QMR is a Single protein structure of sequence from Betula pendula. Full crystallographic information is available from OCA.

Reference

Allergy vaccine engineering: epitope modulation of recombinant Bet v 1 reduces IgE binding but retains protein folding pattern for induction of protective blocking-antibody responses., Holm J, Gajhede M, Ferreras M, Henriksen A, Ipsen H, Larsen JN, Lund L, Jacobi H, Millner A, Wurtzen PA, Spangfort MD, J Immunol. 2004 Oct 15;173(8):5258-67. PMID:15470071

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