3c9j: Difference between revisions

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-[[Image:3c9j.jpg|left|200px]]<br /><applet load="3c9j" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="3c9j, resolution 3.50&Aring;" />
-'''The Crystal structure of Transmembrane domain of M2 protein and Amantadine complex'''<br />
-==Overview==
+==The Crystal structure of Transmembrane domain of M2 protein and Amantadine complex==
-The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.
+<StructureSection load='3c9j' size='340' side='right'caption='[[3c9j]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3c9j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Hong_Kong/156/97(H5N1)) Influenza A virus (A/Hong Kong/156/97(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C9J FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=308:(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DECAN-1-AMINE'>308</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c9j OCA], [https://pdbe.org/3c9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c9j RCSB], [https://www.ebi.ac.uk/pdbsum/3c9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c9j ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/M2_I97A1 M2_I97A1] Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation.
-==About this Structure==
+==See Also==
-C9J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=308:'>308</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:308+Binding+Site+For+Residue+B+101'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C9J OCA].
+*[[Ion channels 3D structures|Ion channels 3D structures]]
+*[[M2 protein|M2 protein]]
-==Reference==
+__TOC__
-Structural basis for the function and inhibition of an influenza virus proton channel., Stouffer AL, Acharya R, Salom D, Levine AS, Di Costanzo L, Soto CS, Tereshko V, Nanda V, Stayrook S, DeGrado WF, Nature. 2008 Jan 31;451(7178):596-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18235504 18235504]
+</StructureSection>
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Acharya, R.]]
+[[Category: Acharya R]]
-[[Category: Salom, D.]]
+[[Category: Salom D]]
-[[Category: Stouffer, A L.]]
+[[Category: Stouffer AL]]
-[[Category: 308]]
-[[Category: ion channel]]
-[[Category: m2-amantadine complex]]
-[[Category: m2tm]]
-[[Category: membrane protein]]
-[[Category: proton channel]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:40:32 2008''