کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508385 | 1537691 | 2017 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Palmitoylation of cysteine 415 of CB1 receptor affects ligand-stimulated internalization and selective interaction with membrane cholesterol and caveolin 1
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کلمات کلیدی
Helix 8CT-BCB1GPCRTMHCRACβ2-ARCCm - CCMG-protein-coupled receptor - G-پروتئین گیرندهCaveolae - حفره غشاییMolecular dynamics - دینامیک ملکولی یا پویایی مولکولیtransmembrane helix - مارپیچ فرابنفشHomology modeling - مدل سازی همگراtype-1 cannabinoid receptor - نوع 1 گیرنده کانابینوئیدtype 1 cannabinoid receptor - نوع 1 گیرنده کانابینوئیدcholera toxin subunit B - کلسترول توکسین Bcholesterol consensus motif - کلسترول رضایت مندانهLipid rafts - گستره چربی، کلک چربی یا لیپید رفتβ2-adrenergic receptor - گیرنده β2-adrenergic
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We previously demonstrated that CB1 receptor is palmitoylated at cysteine 415, and that such a post-translational modification affects its biological activity. To assess the molecular mechanisms responsible for modulation of CB1 receptor function by S-palmitoylation, in this study biochemical and morphological approaches were paralleled with computational analyses. Molecular dynamics simulations suggested that this acyl chain stabilizes helix 8 as well as the interaction of CB1 receptor with membrane cholesterol. In keeping with these in silico data, experimental results showed that the non-palmitoylated CB1 receptor was unable to interact efficaciously with caveolin 1, independently of its activation state. Moreover, in contrast with the wild-type receptor, the lack of S-palmitoylation in the helix 8 made the mutant CB1 receptor completely irresponsive to agonist-induced effects in terms of both lipid raft partitioning and receptor internalization. Overall, our results support the notion that palmitoylation of cysteine 415 modulates the conformational state of helix 8 and influences the interactions of CB1 receptor with cholesterol and caveolin 1, suggesting that the palmitoyl chain may serve as a functional interface for CB1 receptor localization and function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1862, Issue 5, May 2017, Pages 523-532
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1862, Issue 5, May 2017, Pages 523-532
نویسندگان
Sergio Oddi, Tomasz Maciej Stepniewski, Antonio Totaro, Jana Selent, Lucia Scipioni, Beatrice Dufrusine, Filomena Fezza, Enrico Dainese, Mauro Maccarrone,