1qmr
From Proteopedia
(New page: 200px<br /> <applet load="1qmr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qmr, resolution 2.15Å" /> '''BIRCH POLLEN ALLERG...) |
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| - | [[Image:1qmr.gif|left|200px]]<br /> | + | [[Image:1qmr.gif|left|200px]]<br /><applet load="1qmr" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1qmr" size=" | + | |
caption="1qmr, resolution 2.15Å" /> | caption="1qmr, resolution 2.15Å" /> | ||
'''BIRCH POLLEN ALLERGEN BET V 1 MUTANT N28T, K32Q, E45S, P108G'''<br /> | '''BIRCH POLLEN ALLERGEN BET V 1 MUTANT N28T, K32Q, E45S, P108G'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human type 1 immediate allergic response symptoms are caused by mediator | + | 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== | ==About this Structure== | ||
| - | 1QMR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Betula_pendula Betula pendula]. Full crystallographic information is available from [http:// | + | 1QMR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Betula_pendula Betula pendula]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QMR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gajhede, M.]] | [[Category: Gajhede, M.]] | ||
[[Category: Henriksen, A.]] | [[Category: Henriksen, A.]] | ||
| - | [[Category: Holm, J | + | [[Category: Holm, J O.]] |
| - | [[Category: Spangfort, M | + | [[Category: Spangfort, M D.]] |
[[Category: allergen]] | [[Category: allergen]] | ||
[[Category: pathogenesis-related protein]] | [[Category: pathogenesis-related protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:41:25 2008'' |
Revision as of 12:41, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 14:41:25 2008
