TY - JOUR JF - sjimu JO - J. Ilam Uni. Med. Sci. VL - 25 IS - 3 PY - 2017 Y1 - 2017/9/01 TI - Clustering Membrane Helical Residues in the Human Serotonin Transporter TT - دسته بندی اسید ‌های آمینه‌ی هلیکس ‌های غشایی در پروتئین انتقال ‌دهنده ‌‌ی سروتونین انسانی N2 - Introduction: Recently, 6 crystallographic structures of the pharmacologically important human serotonin transporter protein (5-HTT) were reported. In the present survey, two of these crystallographic structures and two homology models were used to study the distribution of 5-HTT’s residues based on their position and orientation. The aim here was to understand the structural and functional roles of membrane helices better in transporters and the costs/benefits of using homology models in such studies. Materials & methods: The membrane helical segments of 5-HTT were identified using a KD-hydropathy plot. The classification of membrane helical residues into 4 groups (Lipid-facing, Lumen-facing, Right and Left) was done using a novel method considering residue positions. Also two 3D structural models of 5-HTT were generated using MODELLER based on templates with 38% and 60% similarities. Findings: Although the majority of hydrophobic residues in membrane helices were in the Lipid-facing cluster, a considerable percentage of them laid within the Lumen-facing cluster. In the Lipid-facing cluster, Ile, Leu, Val, Thr, Ala and Phe were the most frequent residues, respectively. Thus, their 3D positioning patterns were responsible for most of protein-lipid interactions and the functions of these interactions. Discussion & conclusions: Judging by the correlation coefficients, Lipid-facing and Right clusters are the most similar. This suggests that helices may rotate during the outward-inward conformational switch of the transporters. Our model-crystal structure comparisons demonstrate that in the case of membrane transporters, using a template with 38% similarity, results in poor modeling of the membrane helices. These findings can help us understand the structure and function of membrane helices in transporter proteins better. SP - 57 EP - 72 AU - Shariat Panahi, Ali AU - Taghizadeh, Mohammad AU - Goliaei, Bahram AU - Madadkar Sobhani, Armin AD - Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran KW - Residue-level study KW - 5-HTT KW - Homology modeling KW - Membrane helices KW - Membrane transporters UR - http://sjimu.medilam.ac.ir/article-1-4084-en.html DO - 10.29252/sjimu.25.3.57 ER -