دورية أكاديمية

Structural Basis of the Interaction of the G Proteins, Gαi1, Gβ1γ2 and Gαi1β1γ2, with Membrane Microdomains and Their Relationship to Cell Localization and Activity

التفاصيل البيبلوغرافية
العنوان: Structural Basis of the Interaction of the G Proteins, Gαi1, Gβ1γ2 and Gαi1β1γ2, with Membrane Microdomains and Their Relationship to Cell Localization and Activity
المؤلفون: Rafael Álvarez, Pablo V. Escribá
المصدر: Biomedicines; Volume 11; Issue 2; Pages: 557
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2023
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: drug discovery, lipid rafts, membrane lipids, palmitoylation, protein structure, protein prenylation, lipid structure, protein–lipid interactions, membrane microdomain, cell signaling, membrane lipid therapy, melitherapy
الوصف: GPCRs receive signals from diverse messengers and activate G proteins that regulate downstream signaling effectors. Efficient signaling is achieved through the organization of these proteins in membranes. Thus, protein–lipid interactions play a critical role in bringing G proteins together in specific membrane microdomains with signaling partners. Significantly, the molecular basis underlying the membrane distribution of each G protein isoform, fundamental to fully understanding subsequent cell signaling, remains largely unclear. We used model membranes with lipid composition resembling different membrane microdomains, and monomeric, dimeric and trimeric Gi proteins with or without single and multiple mutations to investigate the structural bases of G protein–membrane interactions. We demonstrated that cationic amino acids in the N-terminal region of the Gαi1 and C-terminal region of the Gγ2 subunit, as well as their myristoyl, palmitoyl and geranylgeranyl moieties, define the differential G protein form interactions with membranes containing different lipid classes (PC, PS, PE, SM, Cho) and the various microdomains they may form (Lo, Ld, PC bilayer, charged, etc.). These new findings in part explain the molecular basis underlying amphitropic protein translocation to membranes and localization to different membrane microdomains and the role of these interactions in cell signal propagation, pathophysiology and therapies targeted to lipid membranes.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: Cell Biology and Pathology; https://dx.doi.org/10.3390/biomedicines11020557Test
DOI: 10.3390/biomedicines11020557
الإتاحة: https://doi.org/10.3390/biomedicines11020557Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.6ABECE28
قاعدة البيانات: BASE