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:: Volume 25, Issue 3 (9-2017) ::
sjimu 2017, 25(3): 57-72 Back to browse issues page
Clustering Membrane Helical Residues in the Human Serotonin Transporter
Ali Shariat Panahi Mr.1, Mohammad Taghizadeh Dr. 2, Bahram Goliaei Dr.3, Armin Madadkar Sobhani Dr.3
1- Dept of Cell and Molecular Biology, Tehran University, Tehran, Iran
2- Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran , mtaghizadeh@alumni.ut.ac.ir
3- Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran
Abstract:   (1617 Views)

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.

Keywords: Residue-level study, 5-HTT, Homology modeling, Membrane helices, Membrane transporters
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Type of Study: Research |
Received: 2017/01/15 | Accepted: 2017/05/20 | Published: 2017/09/6
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Shariat Panahi A, Taghizadeh M, Goliaei B, Madadkar Sobhani A. Clustering Membrane Helical Residues in the Human Serotonin Transporter. sjimu. 2017; 25 (3) :57-72
URL: http://sjimu.medilam.ac.ir/article-1-4084-en.html

Volume 25, Issue 3 (9-2017) Back to browse issues page
مجله علمی پزوهشی دانشگاه علوم پزشکی ایلام scientific journal of ilam university of medical sciences
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