کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5131866 1378779 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E
چکیده انگلیسی


- The Cε3 domains of IgE are most susceptible to thermally induced unfolding determined by differential scanning fluorimetry.
- The Cε3 domains are responsible for the characteristically low melting temperature of IgE.
- The Cε3 domains exhibit the greatest intrinsic flexibility.
- Quaternary structural diversity of Cε3 domains is compared across all known structures using a simplified single parameter.
- Human IgE-Fc and Fcε3-4 domain structures are determined at the highest resolutions yet reported (1.75 Å and 2.0 Å).

Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma. Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains. A sub-fragment lacking the Cε2 domains, Fcε3-4, also binds to both receptors, although receptor binding almost exclusively involves the Cε3 domains. This domain also contains the N-linked glycosylation site conserved in other isotypes. We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75 Å and 2.0 Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains. Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc. Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain. A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states. Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1865, Issue 11, Part A, November 2017, Pages 1336-1347
نویسندگان
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