A general procedure for building the transmembrane domains of G‐protein coupled receptors |
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Authors: | Juan J Perez Marta Filizola Maria Caritenì‐Farina |
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Institution: | (1) Dept. d’Enginyeria Quimica, UPC, ETS d’Enginyers Industrials, Av. Diagonal 647, 08028 Barcelona, Spain;(2) Centro di Ricerca Interdipartimentale di Scienze Computazionali e Biotecnologiche (CRISCEB), Seconda Universitá degli Studi di Napoli, Via Costantinopoli 16, 80138 Napoli, Italy |
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Abstract: | The only results available at present about the structural features of G‐protein coupled receptors are the low resolution
electron projection maps obtained from microscopy studies carried out on two‐dimensional crystals of rhodopsin. These studies
support previous suggestions that these integral proteins are constituted by seven transmembrane domains. The low resolution
electron density map of rhodopsin can be used to extract information about helix relative positions and tilt. This information,
together with a reliable procedure to assess the residues involved in each of the transmembrane regions, can be used to construct
a model of rhodopsin at atomic resolution. We have developed an algorithm that can be used to generate such a model in a completely
automated fashion. The steps involved are: (i) locate the centers of the helices according to the low resolution electron
density map; (ii) compute the tilt of each helix based on the elliptical shape observed by each helix in the map; (iii) define
a local coordinate system for each of the helices; (iv) bring them together in an antiparallel orientation; (v) rotate each
helix through the helical axis in such a way that its hydrophobic moment points in the same direction as the bisector formed
between three consecutive helices in the bundle; (vi) rotate each helix through an axis perpendicular to the helical one to
assign a proper tilt; (vii) translate each of the helix to its center deduced from the projection map. A major advantage of
the procedure presented is its generality and consequently can be used to obtain a model of any G‐protein coupled receptor
with the only assumption that the shape of the bundle is the same as found in rhodopsin. This avoids uncertainties found in
other procedures that construct models of G‐protein coupled receptors based on sequence homology using rhodopsin as template.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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