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Design of chimeric proteins by combination of subdomain-sized fragments

Title data

Farías-Rico, José Arcadio ; Höcker, Birte:
Design of chimeric proteins by combination of subdomain-sized fragments.
In: Keating, Amy E. (ed.): Methods in protein design. - Amsterdam : Academic Press , 2013 . - pp. 389-405 . - (Methods in Enzymology ; 523 )
ISBN 978-0-12-394292-0
DOI: https://doi.org/10.1016/B978-0-12-394292-0.00018-7

Abstract in another language

Hybrid proteins or chimeras are generated by recombination of protein fragments. In the course of evolution, this mechanism has led to major diversification of protein folds and their functionalities. Similarly, protein engineers have taken advantage of this attractive strategy to build new proteins. Methods that use homologous recombination have been developed to (semi) randomly create chimeras from which the best can be selected. We wanted to recombine very divergent or even unrelated fragments, which is not possible with these methods. Consequently, based on the observation that nature evolves new proteins also through illegitimate recombination, we developed a strategy to design chimeras using protein fragments from different folds. For this approach, we employ detailed structure comparisons, and based on structural similarities, we choose the fragments used for recombination. Model building and minimization can be used to assess the design, and further optimization can be performed using established computational design methodologies. Here, we outline a general approach to rational protein chimera design based on our experience, and provide considerations for the selection of the fragments, the evaluation, and possible redesign of the constructs.

Further data

Item Type: Article in a book
Refereed: Yes
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry I - Proteinbiochemie der Signaltransduktion
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design > Chair Biochemistry III - Protein Design - Univ.-Prof. Dr. Birte Höcker
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 540 Chemistry
Date Deposited: 24 May 2017 06:50
Last Modified: 26 Nov 2024 14:45
URI: https://eref.uni-bayreuth.de/id/eprint/37239