
The Library
Loop B is a major structural component of the 5-HT3 receptor
Tools
Thompson, Andrew J., Lochner, Martin and Lummis, S. C. R. (2008) Loop B is a major structural component of the 5-HT3 receptor. Biophysical Journal, Vol.95 (No.12). pp. 5728-5736. doi:10.1529/biophysj.108.135624 ISSN 0006-3495.
![]()
|
PDF
WRAP_Thompson_Loop_B.pdf - Requires a PDF viewer. Download (1276Kb) |
Official URL: http://dx.doi.org/10.1529/biophysj.108.135624
Abstract
The 5-HT3 receptor belongs to a family of therapeutically important neurotransmitter-gated receptors whose ligand binding sites are formed by the convergence of six peptide loops (A-F). Here we have mutated 15 amino acid residues in and around loop B of the 5-HT3 receptor (Ser-177 to Asn-191) to Ala or a residue with similar chemical properties. Changes in [3H]granisetron binding affinity (Kd) and 5-HT EC50 were determined using receptors expressed in human embryonic kidney 293 cells. Substitutions at all but one residue (Thr-181) altered or eliminated binding for one or both mutants. Receptors were nonfunctional or EC50 values were altered for all but two mutants (S182T, I190L). Homology modeling indicates that loop B contributes two residues to a hydrophobic core that faces into the β-sandwich of the subunit, and the experimental data indicate that they are important for both the structure and the function of the receptor. The models also show that close to the apex of the loop (Ser-182 to Ile-190), loop B residues form an extensive network of hydrogen bonds, both with other loop B residues and with adjacent regions of the protein. Overall, the data suggest that loop B has a major role in maintaining the structure of the region by a series of noncovalent interactions that are easily disrupted by amino acid substitutions.
Item Type: | Journal Article | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Serotonin, Neurotransmitter receptors, Homology theory, Hydrophobic surfaces | ||||
Journal or Publication Title: | Biophysical Journal | ||||
Publisher: | Biophysical Society | ||||
ISSN: | 0006-3495 | ||||
Official Date: | 15 December 2008 | ||||
Dates: |
|
||||
Volume: | Vol.95 | ||||
Number: | No.12 | ||||
Page Range: | pp. 5728-5736 | ||||
DOI: | 10.1529/biophysj.108.135624 | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Funder: | Wellcome Trust (London, England), Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Swiss National Science Foundation] (SNSF) | ||||
Grant number: | PA00A-105073 (SNSF) |
Request changes or add full text files to a record
Repository staff actions (login required)
![]() |
View Item |
Downloads
Downloads per month over past year