BH3-ONLY PROTEINS - FROM STRUCTURE TO FUNCTION

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Authors

IONESCU Crina-Maria KLÍMOVÁ Zuzana SEHNAL David SVOBODOVÁ VAŘEKOVÁ Radka KOČA Jaroslav

Year of publication 2012
Type Appeared in Conference without Proceedings
MU Faculty or unit

Faculty of Science

Citation
Description Disfunctions in the mechanism of programmed cell death (apoptosis) are directly related to cancer, neurodegenerative and auto-immune diseases. Apoptosis is highly regulated by the interplay of BH3-only proteins [1,2]. How these proteins perform their function at the molecular level is not yet understood, which makes it very hard to develop medical treatment. We recently developed SiteBinder, an effective tool for comparing the 3D structure of multiple protein motifs [3]. Using this tool, we performed a brief structural comparison of the BH3 domain of several BH3-only proteins known to promote cell death. The preliminary results showed that there is a detectable structural trend which correlates with the type of mechanism of action (direct versus indirect) of these proteins. We present here our results of an extensive structural comparison analysis comprising all BH3-only proteins whose structure is known. Our investigations were ultimately meant to determine whether the measures of 3D structural similarity correlate with specificity of binding. The results of our analysis can be useful in studies focused on modulating apoptosis and related diseases.
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