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Protein-Protein and...
Protein-Protein and Protein-Membrane Interactions Regarding the Erbb2/Trastuzumab-Fab Complexes. A Coarse-Grained Molecular Dynamics Description
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- Franco-Gonzalez, Juan F. (författare)
- BIOPHYM, IEM, CSIC, Madrid, Spain
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- Cruz, Victor (författare)
- BIOPHYM, IEM, CSIC, Madrid, Spain
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- Ramos, Javier (författare)
- BIOPHYM, IEM, CSIC, Madrid, Spain
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- Martinez-Salazar, Javier (författare)
- BIOPHYM, IEM, CSIC, Madrid, Spain
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 666-667
- Relaterad länk:
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http://www.sciencedi...
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- ErbB2 is a member of epidermal growth factor receptor (EGFR) family and is overexpressed in many cancers. Specifically, Trastuzumab, which is a monoclonal antibody, is used against ErbB2, but its action mechanism is still unknown. ErbB2 can exist as both monomers and Homodimers, suggesting that Trastuzumab mechanims may be subtle. On the other hand, the membrane plays a role in the action mechanism of Trastuzumab but generates difficulties for structural studies. Coarse-Grained Molecular Dynamics has been used to study the influence of the Trastuzumab on the protein-protein and protein-membrane interactions of the full ErbB2 receptor. Our simulations start from conformations which both extracelullar and intracelullar domains are extended. The results show in both monomers and homodimers systems a folded conformation on the membrane: several experimental results, mainly obtained on ErbB1 support them. The protein-protein interaction on transmembrane and juxtamembrane domains are disrupted on the dimer and disordered on the monomer by the Trastuzumab effect, therefore, the dimerization-driven activation are unfavourable. We present a detailed description of the type of interactions governing the homodimerization and antobody complexation phenomena and the role that the membrane plays on that.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
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