کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1944907 1053244 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional impact of serial deletions at the C-terminus of the human GABAρ1 receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Functional impact of serial deletions at the C-terminus of the human GABAρ1 receptor
چکیده انگلیسی

GABAρ1 receptors are formed by homopentameric assemblies that gate a chloride ion-channel upon activation by the neurotransmitter. Very little is known about the structural and functional roles played by the different domains that form each subunit; but one of them, the fourth transmembrane segment (TM4), is known to form a hydrophobic bundle together with three other TM segments that are necessary to stabilize the structure of the receptor. In this study we progressively removed amino acid residues from the C-terminus of the human GABAρ1 and studied the functional properties of the receptor mutants expressed in X. laevis oocytes. We found that deletions of up to the last four residues gave rise to receptors that were still functional, generating currents of 3.92 µA for the wt, 5.75 μA for S479X, 1.82 μA for F478X, 0.52 μA for I477X and 0.27 μA for S476X when exposed to 5 µM GABA; surprisingly, the mutant with one residue removed resulted more sensitive to the agonists. Further deletions, up to residue W475, resulted in receptors that did not gate an ion-channel. In addition, deleting the signal sequence, from R2-A15, in the N-terminus produced non-functional receptors. This study reveals that GABAρ1 can tolerate removal of several residues that form the fourth transmembrane segment up to a critical point, signaled by W475, beyond which the mutant protein is translated but does not form functional receptors. A comparative study is presented of some electrophysiological and pharmacological properties of the deletion mutants that were able to generate GABA currents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1798, Issue 5, May 2010, Pages 1002–1007
نویسندگان
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