Microbiology and Immunology 4300A Lecture 4: Antiviral PRRs
22 Dec 2019
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Tlr3 expressed inimmuneandnon immunecells dsrnabindstotheconvexlateralsidesof tlr3 dsrna isrigidenoughtostabilizethetlr3homodimerization dsrnashouldbe 90bplong. Tlr7and 8 tlr7 ishighlyexpressed inpdcswhiletlr8 isexpressed in monocytesand dcs. Tlr9 wellexpressedin monocytes bcellsanddcs binds to anmethylated cpgdnasinphagolysosomes. All endosomaltlrsinduceexpressionoftype1 ifns by activating the 1raf316 irf317signalingaxis. Cytoplasmic rna sensing prrsi rig i likereceptors crlrs: rlg l retinoicacid induciblegene1 andmda5 melanoma differentiation associatedgene5 bothhavesimilarmolecularstructure. Bind to 5 end of rna uncapped5 ppprna or 5 p rnas by productsof rnasel binds tothephosphategroupof thephosphorylated 5 end bindsto longdsrna doesnotbindssrna. Mostof our rna issinglestranded if it couldbindto ssrna it wouldalwaysbeactivated. Undergoes 5 endmodification 7 methylguanosinecapping cap preventsbindingofrig i. Alrsareafamilyofdnasensingreceptorsidentifiedamongthehin 200 protein hematopoietic interferon induciblenuclearproteinwith a 200amino acid repeat. A hexamericaim2 unit caninitiateasc filamentation thatinducescaspase l activation. Two lobeslinkedbyfairly flat slightlyconcave platform thatbinds nucleotides cgashasaprotrusion 367 382aminoacids coordinatingzn2 ion known as a zinc loop or thumb. Not present inoas1 canbind13formdna hasmajorandminorgrooves bindsthemajorgroove notpresentin rna. Oasl bindsdsrna dsrna or dsdnabindstothespinalregionleadingto a conformational change binding ofdsrna tooas1 or dsdnato cgasinducesconformational changes inthelobes.
