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The transmembrane domain of the oncogenic mutant ErbB-2 receptor: A structure obtained from site-specific infrared dichroism and molecular dynamics
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Beevers, Andrew J. and Kukol, Andreas. (2006) The transmembrane domain of the oncogenic mutant ErbB-2 receptor: A structure obtained from site-specific infrared dichroism and molecular dynamics. Journal of Molecular Biology, Vol.361 (No.5). pp. 945-953. ISSN 0022-2836
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Official URL: http://dx.doi.org/10.1016/j.jmb.2006.07.004
Abstract
ErbB-2 is a member of the family of epidermal growth factor receptors, which shows an oncogenic mutation in the rat gene neu, Val664Glu in the transmembrane domain that causes permanent dimerisation and subsequently leads to uncontrollable cell division and tumour formation. We have obtained the a-helical structure of the mutant transmembrane domain dimer experimentally with site-specific infrared dichroism (SSID) based on six transmembrane peptides with (CO)-C-13-O-18 carbonyl group-labelled residues. The derived orientational data indicate a local helix tilt ranging from 28(6) to 22(4). Altogether using orientational constraints from SSID and experimental a-helical constraints while performing a systematic conformational search including molecular dynamics simulation in a lipid bilayer, we have obtained a unique experimentally defined atomic structure. The resulting structure consists of a right handed a-helical bundle with the residues Ile659, Val663, Leu667, Ile671, Val674 and Leu679 in the dimerisation interface. The right-handed bundle is in contrast to the left-handed structures obtained in previous modelling efforts. In order to facilitate tight helical packing, the spacious Glu664 residues do not interact directly but with water molecules that enter the bilayer. (c) 2006 Elsevier Ltd. All rights reserved.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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| Divisions: | Faculty of Science > Chemistry Faculty of Science > Molecular Organisation and Assembly in Cells (MOAC) |
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| Journal or Publication Title: | Journal of Molecular Biology | ||||
| Publisher: | Academic Press | ||||
| ISSN: | 0022-2836 | ||||
| Official Date: | 1 September 2006 | ||||
| Dates: |
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| Volume: | Vol.361 | ||||
| Number: | No.5 | ||||
| Number of Pages: | 9 | ||||
| Page Range: | pp. 945-953 | ||||
| Identification Number: | 10.1016/j.jmb.2006.07.004 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| URI: | http://wrap.warwick.ac.uk/id/eprint/33097 |
Data sourced from Thomson Reuters' Web of Knowledge
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