Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model
المؤلفون المشاركون
Schneider, B.
Černý, Jiří
Biedermannová, Lada
Mikulecký, Pavel
Zahradník, Jiří
Charnavets, Tatsiana
Šebo, Peter
المصدر
العدد
المجلد 2015، العدد 2015 (31 ديسمبر/كانون الأول 2015)، ص ص. 1-12، 12ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2015-04-28
دولة النشر
مصر
عدد الصفحات
12
التخصصات الرئيسية
الملخص EN
Combining computational and experimental tools, we present a new strategy for designing high affinity variants of a binding protein.
The affinity is increased by mutating residues not at the interface, but at positions lining internal cavities of one of the interacting molecules.
Filling the cavities lowers flexibility of the binding protein, possibly reducing entropic penalty of binding.
The approach was tested using the interferon-γ receptor 1 (IFNγR1) complex with IFNγ as a model.
Mutations were selected from 52 amino acid positions lining the IFNγR1 internal cavities by using a protocol based on FoldX prediction of free energy changes.
The final four mutations filling the IFNγR1 cavities and potentially improving the affinity to IFNγ were expressed, purified, and refolded, and their affinity towards IFNγ was measured by SPR.
While individual cavity mutations yielded receptor constructs exhibiting only slight increase of affinity compared to WT, combinations of these mutations with previously characterized variant N96W led to a significant sevenfold increase.
The affinity increase in the high affinity receptor variant N96W+V35L is linked to the restriction of its molecular fluctuations in the unbound state.
The results demonstrate that mutating cavity residues is a viable strategy for designing protein variants with increased affinity.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Černý, Jiří& Biedermannová, Lada& Mikulecký, Pavel& Zahradník, Jiří& Charnavets, Tatsiana& Šebo, Peter…[et al.]. 2015. Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model. BioMed Research International،Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1056481
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Černý, Jiří…[et al.]. Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model. BioMed Research International No. 2015 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1056481
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Černý, Jiří& Biedermannová, Lada& Mikulecký, Pavel& Zahradník, Jiří& Charnavets, Tatsiana& Šebo, Peter…[et al.]. Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1056481
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1056481
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر