Publication year
2004Author(s)
Publisher
S.l. : s.n.
ISBN
9064648158
Number of pages
167 p.
Annotation
RU Radboud Universiteit Nijmegen, 01 november 2004
Promotor : Hilbers, C.W. Co-promotores : Vuister, G.W., Hendriks, W.J.A.J.
Publication type
Dissertation
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Organization
Biophysical Chemistry
Subject
Biophysical ChemistryAbstract
Small changes in a protein can significantly affect its function. One particular PDZ domain in the protein PTP-BL can bind to several C termini, each with different amino acid sequences (J Mol. Biol. 2002 Mar 8;316(5):1101-10). A natural splice variant of the same protein domain contains five extra amino acids, which extend a flexible loop on the protein's surface. This causes the splice variant to lose its ability bind to protein C termini but surprisingly, not by obstructing the binding pocket. The structure solved by Walma et al. (Structure (Camb). 2004 Jan;12(1):11-20) shows the insertion alters the internal packing of the protein domain, causing it to become more flexible, and changing the geometry of the the binding pocket, making it too narrow and shallow to accomodate C-termini. Walma et al. extended these results to show that the interaction strength of PDZ domains can be predicted without actually determining their structures. This knowledge is useful, because it typically takes 6 months to a year to determine a protein structure. It remains unclear what the function of this longer PDZ domain is, if it has any at all. Scientists know that the critical feature of a protein is its ability to adopt the right shape for carrying out a particular function. The alternative PDZ2 splice variant is an example of nature's ingenious method to modulate the functional properties of this domain. Illuminating the structure-function relationships of proteins paves the way for the development of new agents and devices to treat disease.
This item appears in the following Collection(s)
- Academic publications [245050]
- Dissertations [13773]
- Faculty of Science [37364]
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