2n70

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(Difference between revisions)

Revision as of 06:27, 26 July 2016

Two-fold symmetric structure of the 18-60 construct of S31N M2 from Influenza A in lipid bilayers

Structural highlights

2n70 is a 4 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[M2_I72A2] 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 (By similarity).^[1]

Publication Abstract from PubMed

We report a magic angle spinning (MAS) NMR structure of the drug-resistant S31N mutation of M218-60 from Influenza A. The protein was dispersed in diphytanoyl-sn-glycero-3-phosphocholine lipid bilayers, and the spectra and an extensive set of constraints indicate that M218-60 consists of a dimer of dimers. In particular, approximately 280 structural constraints were obtained using dipole recoupling experiments that yielded well-resolved (13)C-(15)N, (13)C-(13)C, and (1)H-(15)N 2D, 3D, and 4D MAS spectra, all of which show cross-peak doubling. Interhelical distances were measured using mixed (15)N/(13)C labeling and with deuterated protein, MAS at omegar/2pi = 60 kHz, omega0H/2pi = 1000 MHz, and (1)H detection of methyl-methyl contacts. The experiments reveal a compact structure consisting of a tetramer composed of four transmembrane helices, in which two opposing helices are displaced and rotated in the direction of the membrane normal relative to a four-fold symmetric arrangement, yielding a two-fold symmetric structure. Side chain conformations of the important gating and pH-sensing residues W41 and H37 are found to differ markedly from four-fold symmetry. The rmsd of the structure is 0.7 A for backbone heavy atoms and 1.1 A for all heavy atoms. This two-fold symmetric structure is different from all of the previous structures of M2, many of which were determined in detergent and/or with shorter constructs that are not fully active. The structure has implications for the mechanism of H(+) transport since the distance between His and Trp residues on different helices is found to be short. The structure also exhibits two-fold symmetry in the vicinity of the binding site of adamantyl inhibitors, and steric constraints may explain the mechanism of the drug-resistant S31N mutation.

Structure and Mechanism of the Influenza A M218-60 Dimer of Dimers.,Andreas LB, Reese M, Eddy MT, Gelev V, Ni QZ, Miller EA, Emsley L, Pintacuda G, Chou JJ, Griffin RG J Am Chem Soc. 2015 Dec 2;137(47):14877-86. doi: 10.1021/jacs.5b04802. Epub 2015 , Aug 31. PMID:26218479^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Holsinger LJ, Nichani D, Pinto LH, Lamb RA. Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol. 1994 Mar;68(3):1551-63. PMID:7508997
↑ Andreas LB, Reese M, Eddy MT, Gelev V, Ni QZ, Miller EA, Emsley L, Pintacuda G, Chou JJ, Griffin RG. Structure and Mechanism of the Influenza A M218-60 Dimer of Dimers. J Am Chem Soc. 2015 Dec 2;137(47):14877-86. doi: 10.1021/jacs.5b04802. Epub 2015 , Aug 31. PMID:26218479 doi:http://dx.doi.org/10.1021/jacs.5b04802

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n70"

@@ Line 1: / Line 1: @@
 ==Two-fold symmetric structure of the 18-60 construct of S31N M2 from Influenza A in lipid bilayers==
 <StructureSection load='2n70' size='340' side='right' caption='[[2n70]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2n70]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N70 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N70 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n70 OCA], [http://pdbe.org/2n70 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n70 RCSB], [http://www.ebi.ac.uk/pdbsum/2n70 PDBsum]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n70 OCA], [http://pdbe.org/2n70 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n70 RCSB], [http://www.ebi.ac.uk/pdbsum/2n70 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n70 ProSAT]</span></td></tr>
 </table>
 == Function ==

2n70

From Proteopedia

Revision as of 06:27, 26 July 2016

Two-fold symmetric structure of the 18-60 construct of S31N M2 from Influenza A in lipid bilayers

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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