| Title: | Postulates for validating TLR4 agonists |
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| Authors: | ID Manček Keber, Mateja (Author)
ID Jerala, Roman (Author) |
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| Files: |  URL - Source URL, visit http://onlinelibrary.wiley.com/doi/10.1002/eji.201444462/pdf
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| Language: | English |
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| Typology: | 1.02 - Review Article |
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| Organization: |  KI - National Institute of Chemistry
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| Abstract: | TLRs play a central role in the innate immune response, recognizing a variety of molecular
structures characteristic of pathogens. Although TLR4, together with its co-receptor
myeloid differentiation-2 (MD-2), recognize bacterial LPS and therefore Gram-negative
bacterial infections, it also plays a key role in many other pathophysiological processes,
including sterile inflammation and viral infection. Specifically, numerous endogenous
agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have
been reported. Direct activation of a single receptor by such a range of molecular signals
is very difficult to explain from a structural and mechanistic point of view. It is likely
that only a subset of these directly activate the TLR4–MD-2 complex. We propose three
postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators.
These postulates are as follows: (i) that the agonist requires the TLR4/MD-2 receptor complex;
(ii) that agonist formed synthetically or in situ must activate the receptor complex
in order to eliminate artifacts of contamination by other agonists; and (iii) that a specific
molecular interaction between the agonist and TLR4/MD-2 must be identified. The same
type of postulates can be applied to pattern recognition receptors in general. |
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| Keywords: | TLR4 agonists, molecular mechanism, ligand recognition |
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| Publication status: | Published |
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| Year of publishing: | 2015 |
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| Number of pages: | str. 356-370 |
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| Numbering: | Vol. 45, iss. 2 |
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| PID: | 20.500.12556/DiRROS-762  |
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| UDC: | 577.2 |
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| ISSN on article: | 0014-2980 |
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| DOI: | 10.1002/eji.201444462 |
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| COBISS.SI-ID: | 5617434 |
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| Publication date in DiRROS: | 26.01.2015 |
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| Views: | 5399 |
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| Downloads: | 564 |
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