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Structure function relationship in active and inactive Apaf-۱ in apoptosome formation

عنوان مقاله: Structure function relationship in active and inactive Apaf-۱ in apoptosome formation
شناسه ملی مقاله: BIOCONF21_0540
منتشر شده در بیست و یکمین کنگره ملی و نهمین کنگره بین المللی زیست شناسی ایران در سال 1399
مشخصات نویسندگان مقاله:

Saman Hosseinkhani - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University. Tehran, Iran
Ali-Reza Noori - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University. Tehran, Iran
Maryam Nikkhah - Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University. Tehran, Iran

خلاصه مقاله:
In multicellular organism, apoptosis is one of the programmed cells death pathway in which is vital for development and regulation of homeostasis. During apoptosis and other programmed cell death pathways formation of large protein complexes is one of the main hallmarks. We have used split luciferase complementary assay to monitor protein-protein interactions in mentioned complexes like apoptosome, necrosome and inflammasome. During apoptosis, apoptosome formation is the main bottleneck for cell death progress, in which Apaf-۱ is an adaptor that activates caspase-۹. Structural studies suggest that normally Apaf-۱ is held in an inactive conformation (Latent form) by intramolecular interactions between Apaf-۱’s nucleotide binding domain and one of its WD۴۰ domains (WD۱). Based on molecular model of Apaf-۱ activation, cytochrome cbinds to sites in WD۱ and in Apaf-۱’s second WD۴۰ domain (WD۲), moving WD۱ and WD۲ closer together that allows Apaf-۱ to bind dATP or ATP and to form the apoptosome then activates caspase-۹. We investigated the effect of one WD domain (Apaf-۱ ۱-۹۲۱) deletion on Apaf-۱ interactions and caspase cascade activation. Trucated Apaf-۱ (۱-۹۲۱) could not activate caspase-۹, even in the presence of cytochrome c that suggest a single WD domain is sufficient to lock Apaf-۱ in an inactive state and that this state cannot be altered by cytochrome c.

صفحه اختصاصی مقاله و دریافت فایل کامل: https://civilica.com/doc/1260507/