کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1945174 | 1053255 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Comparative modeling of the quaternary structure for the human TRPM8 channel and analysis of its binding features
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The aim of this study was to generate a reliable model for the homotetrameric structure of the human TRPM8 cation channel, a temperature sensor involved in innocuous cold perceptions. The described model was generated using a fragmental strategy and its interaction capacities were explored by docking a representative set of ligands. The analysis of the quaternary structure suggests that the N-terminus possesses a solenoidal topology which could be involved in tetramerization due to its electrostatic characteristics. Again, the tetramer model unveils a precise fitting between the segments of neighbouring monomers affording attractive suggestions for the multifaceted mechanism of channel gating. Docking results are in convincing agreement with mutational analyses and confirm that S4 and S4-S5 linker play a key role in channel activation. Overall, the proposed model could find fertile applications to further investigate the gating mechanism and to design truly selective ligands able to clarify the pathophysiological roles of the TRPM8 channel.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1788, Issue 5, May 2009, Pages 973-982
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1788, Issue 5, May 2009, Pages 973-982
نویسندگان
Alessandro Pedretti, Cristina Marconi, Ilaria Bettinelli, Giulio Vistoli,