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2jrw

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Revision as of 07:02, 11 July 2018

Solution structure of Cyclic extended Pep1(Cyc.ext.Pep.1) for autoimmune myasthenia gravis

Structural highlights

2jrw is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2jrv
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Myasthenia gravis (MG) and its animal model, experimental MG (EAMG), are autoimmune disorders in which major pathogenic antibodies are directed against the main immunogenic region (MIR) of the nicotinic acetylcholine receptor (nAChR). In an earlier attempt to develop peptide mimotopes capable of preventing the anti-MIR-mediated pathogenicity, the peptide Pep.1 was initially identified from phage display, and subsequently, Cyclic extended Pep.1 (Cyc.ext.Pep.1), which incorporates eight additional residues into the Pep.1 sequence and has an affinity for the anti-MIR antibody mAb198 3 orders of magnitude greater than that of Pep.1, was developed. In an animal model, Pep.1 shows no ability to inhibit mAb198-induced EAMG, whereas Cyc.ext.Pep.1 successfully blocks anti-MIR antibody 198 (mAb198)-induced EAMG. Our aim in this study was to identify the structural characteristics related to the different affinities for mAb198 of Pep.1 and Cyc.ext.Pep.1 using NMR spectroscopy and alanine scanning analysis. The NMR structural analysis revealed that Pep.1 is very flexible in solution, whereas Cyc.ext.Pep.1 is highly rigid within a region containing several turn structures. Interestingly, TRNOE experiments revealed that mAb198-bound Pep.1, particularly in the region between Asn7 and Glu11, shows significant structural similarity to the region between Asn10 and Glu14 of Cyc.ext.Pep.1, which is critical for interaction with mAb198. We therefore conclude the higher affinity of Cyc.ext.Pep.1 for mAb198 reflects the fact that incorporation of additional residues producing a single disulfide bond endows Pep.1 with a conformational rigidity that mimics the structure of mAb198-bound Pep.1. Furthermore, our results suggest that cyclic extended peptides could be utilized generally as useful tools to optimize the affinity of phage library-derived peptide antigens.

Structural analysis of immunotherapeutic peptides for autoimmune Myasthenia gravis.,Jung HH, Yi HJ, Lee SK, Lee JY, Jung HJ, Yang ST, Eu YJ, Im SH, Kim JI Biochemistry. 2007 Dec 25;46(51):14987-95. Epub 2007 Dec 1. PMID:18052043^[1]

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

References

↑ Jung HH, Yi HJ, Lee SK, Lee JY, Jung HJ, Yang ST, Eu YJ, Im SH, Kim JI. Structural analysis of immunotherapeutic peptides for autoimmune Myasthenia gravis. Biochemistry. 2007 Dec 25;46(51):14987-95. Epub 2007 Dec 1. PMID:18052043 doi:10.1021/bi701298b

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

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 ==Solution structure of Cyclic extended Pep1(Cyc.ext.Pep.1) for autoimmune myasthenia gravis==
 <StructureSection load='2jrw' size='340' side='right' caption='[[2jrw]], [[NMR_Ensembles_of_Models | 16 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2jrw]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JRW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JRW FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jrv|2jrv]]</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=2jrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jrw OCA], [http://pdbe.org/2jrw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jrw RCSB], [http://www.ebi.ac.uk/pdbsum/2jrw PDBsum]</span></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=2jrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jrw OCA], [http://pdbe.org/2jrw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jrw RCSB], [http://www.ebi.ac.uk/pdbsum/2jrw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jrw ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">

2jrw

From Proteopedia

Revision as of 07:02, 11 July 2018

Solution structure of Cyclic extended Pep1(Cyc.ext.Pep.1) for autoimmune myasthenia gravis

Structural highlights

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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