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  Convergence of experimental, computational and evolutionary approaches predicts the presence of a tetrameric form for CD3-zeta

Torres, J., Briggs, J. A. G., & Arkin, I. T. (2002). Convergence of experimental, computational and evolutionary approaches predicts the presence of a tetrameric form for CD3-zeta. Journal of Molecular Biology, 316(2), 375-384. doi:10.1006/jmbi.2001.5268.

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Torres, J., Author
Briggs, John A. G.1, Author           
Arkin, I. T., Author
Affiliations:
1University of Oxford, External Organizations, Oxford, UK, ou_3346844              

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Free keywords: membrane proteins molecular dynamics molecular modelling site-specific infrared dichroism CD3-zeta transmembrane alpha-helices zeta-chain dimerization phospholamban identification receptors channel antigen domain motif Biochemistry & Molecular Biology
 Abstract: Experimental results using multiple site-specific infrared dichroism have shown that, when reconstituted into lipid bilayers, the orientation of the transmembrane domain of CD3-zeta is not compatible with a dimeric right-handed model reported previously. This model, obtained using a Computational approach that uses evolutionary data, is in agreement with mutagenesis data and homology modelling. This suggested that, in our experimental conditions, the oligomeric state of CD3-zeta may not be dimeric. We have explored this possibility by performing global searching molecular dynamics simulations assuming different homo-oligomeric sizes (from 2 to 6). In these simulations, the helix tilt was restrained to the average helix tilt obtained experimentally, 12 degrees. Only a left-handed tetrameric model was compatible with the experimentally observed tilt and rotational orientation of the helix, and was also the lowest-energy model amongst the candidate structures obtained. Furthermore, simulations performed using close homologues demonstrate that this model is compatible with evolutionary conservation data. Finally, the pattern of residue conservation in the family of proteins strongly argues in favour of the presence of a left-handed hetero-oligomer with an orientation compatible with the tetramer we present. These results show that both the known dimeric and the so far undetected tetrameric form may be of functional importance in the cell. (C) 2002 Elsevier Science Ltd.

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Language(s): eng - English
 Dates: 2002
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: WOS:000174108100014
DOI: 10.1006/jmbi.2001.5268
ISSN: 0022-2836
 Degree: -

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Title: Journal of Molecular Biology
  Alternative Title : J. Mol. Biol.
Source Genre: Journal
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Pages: - Volume / Issue: 316 (2) Sequence Number: - Start / End Page: 375 - 384 Identifier: -