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MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. [5] MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2 , and functions as a pattern recognition receptor capable of detecting viruses .
RIG-I domain architecture. (A) Schematic representation of full-length RIG-I. (B) X-ray crystal structure of RNA-bound RIG-I ( ), excluding the CARD domains.The RLR receptors are members of the DEAD-box (SF2) helicase family (despite containing a DExD/H motif, rather than the DEAD motif characteristic of the family) and share a common domain architecture.
The MD5 message-digest algorithm is a widely used hash function producing a 128-bit hash value. MD5 was designed by Ronald Rivest in 1991 to replace an earlier hash function MD4, [3] and was specified in 1992 as RFC 1321.
MDA5, an RNA helicase, is known to be activated by complex high molecular weight dsRNA transcribed from the viral genome. [13] [14] In a cell with RNase L, MDA5 activity may be further enhanced. [13] When active, RNase L cleaves and identifies viral RNA and feeds it into MDA5 activation sites, enhancing the production of IFN-β.
At a resting state for the cell, a protein called mitofusin 2 (MFN2) is known to interact with MAVS, preventing MAVS from binding to the cytosolic proteins, such as RIG-I and MDA5. [ 7 ] [ 8 ] Upon recognition of the virus in the cytosol, mitochondria-associated ER membranes (MAM) and mitochondria will become physically tethered by MFN2 and RIG ...
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The main symptoms include several kinds of skin rash along with muscle weakness in both upper arms or thighs. [8] Although dermatomyositis is closely related to polymyositis and is sometimes assumed to be a complication of that disease, most patients with dermatomyositis develop skin symptoms before any muscle involvement.
There is very little known about the mechanism of action of these drugs. However, it was shown in 2015 that a possible mechanism of action of these drugs in colorectal cancer-initiating cells is through activating dsRNA expression which leads to the activation of the MDA5/MAVS RNA recognition pathway inducing some sort of viral mimicry inside the cell.