Publication: Heterotrimerik G Proteinleri
Abstract
G proteinleri olarak bilinen heterotrimerik G proteinleri, bakterilerden memelilere kadar korunmuş büyük GTPaz ailesinin üyelerindendir. G proteinleri plazma zarındaki hücre yüzeyi reseptörleri ve efektörleri ile kenetlenerek hücresel sinyal iletisinde önemli roller üstlenirler. G proteinleri GTP’nin bağlandığı ve hidrolizlendiği bir α-altbirimi ile bir βγ-kompleksinden oluşmaktadır. Bugüne kadar 20 farklı α-altbirimi, 5 β-altbirimi ve 14 γ-alttipi tanımlanmıştır. G protein heterotrimerleri, α-altbirimlerinin birincil dizilimlerine göre sınıflandırılır ve 4 aileye ayrılırlar. G proteinleri inaktif (sessiz) durumdayken, GDP bağlı α altbirimi ile βγ altbirimleri birbirlerine sıkıca bağlı bir heterotrimerdir. Reseptör aktivasyonu, GDP’nin GTP ile yer değiştirmesini uyarır ve hemen arkasından βγ altbirimleri, α-altbiriminden ayrılır. αGTP ve βγ kompleksinin herikiside özgün efektörler ile etkileşir ve düzenler. G protein α- ve βγ altbirimleri fosforillenme, miristoillenme palmitoillenme ve prenillenme gibi translasyon sonrası uyarlamalarla düzenlenir. G protein α- ve βγ altbirimleri çeşitli efektörlerin aktivitelerini düzenler. G proteinleri duysal algılama, nöronal etkinlik ve hormonal düzenleme gibi pekçok hücresel yanıtın oluşumuna aracılık eder. Son zamanlarda, GPCR’lerin ve G proteinlerinin hücre büyümesi, farklılaşması ve hücresel transformasyon ile ilişkili olduğu bildirilmiştir.
Heterotrimeric G proteins, commonly known as G proteins are members of the large GTPase superfamily that are conserved from bacteria to mammals. G proteins play an essential role in cellular signaling by coupling many cell surface receptors to effectors on the plasma membrane. G proteins are composed of an α-subunit that binds and hydrolyzes GTP and a βγ-subunit complex. To date over 20 different α subunits, 5 β subunits and 14 γ subtypes have been defined. Classification of G protein heterotrimers are based on the primary sequences of their α-subunits, resulting in four main families. In its inactive state, each G protein is a heterotimer in which the GDP bound α chain is tightly associated with the βγ subunits. Receptor activation promotes the replacement of GDP by GTP and the consequent dissociation of α from βγ. Both αGTP and the βγ complex interact with and regulate specific effectors. Activation is then terminated by the intrinsic GTPase activity of the α chain, which returns the protein to its inactive state. G proteins are regulated by posttranslational modifications including phosphorylation, myristoylation, palmitoylation, and prenylation of Gα- and Gβγ- subunits. G protein α- and βγ- subunits regulate the activities of diverse effectors. G proteins mediate a wide variety of cellular responses, including sensory perception, neuronal activity and hormonal regulation. Recent reports indicate that GPCRs and G proteins are also involved in the regulation of cell growth, differentiation and cellular transformation.
Heterotrimeric G proteins, commonly known as G proteins are members of the large GTPase superfamily that are conserved from bacteria to mammals. G proteins play an essential role in cellular signaling by coupling many cell surface receptors to effectors on the plasma membrane. G proteins are composed of an α-subunit that binds and hydrolyzes GTP and a βγ-subunit complex. To date over 20 different α subunits, 5 β subunits and 14 γ subtypes have been defined. Classification of G protein heterotrimers are based on the primary sequences of their α-subunits, resulting in four main families. In its inactive state, each G protein is a heterotimer in which the GDP bound α chain is tightly associated with the βγ subunits. Receptor activation promotes the replacement of GDP by GTP and the consequent dissociation of α from βγ. Both αGTP and the βγ complex interact with and regulate specific effectors. Activation is then terminated by the intrinsic GTPase activity of the α chain, which returns the protein to its inactive state. G proteins are regulated by posttranslational modifications including phosphorylation, myristoylation, palmitoylation, and prenylation of Gα- and Gβγ- subunits. G protein α- and βγ- subunits regulate the activities of diverse effectors. G proteins mediate a wide variety of cellular responses, including sensory perception, neuronal activity and hormonal regulation. Recent reports indicate that GPCRs and G proteins are also involved in the regulation of cell growth, differentiation and cellular transformation.