Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Since the first determination of structure of the HLA-A2 complex, >200 MHC/peptide structures have been recorded, whereas the available T cell receptor (TCR)/peptide/MHC complex structures now are <20. Among these structures, only six are TCR/peptide/MHC Class II (MHCII) structures. The most recent of these structures, obtained by using TCR-Ob.1A12 from a multiple sclerosis patient and the MBP85-99/HLA-DR2 complex, was very unusual in that the TCR was located near the N-terminal end of the peptide-binding cleft of the MHCII protein and had an orthogonal angle on the peptide/MHC complex. The unusual structure suggested the possibility of a disturbance of its signaling capability that could be related to autoimmunity. Here, homology modeling and a new simulation method developed for TCR/peptide/MHC docking have been used to examine the positioning of the complex of two additional TCRs obtained from the same patient (TCR-Ob.2F3 or TCR-Ob.3D1 with MBP85-99/HLA-DR2). The structures obtained by this simulation are compatible with available data on peptide specificity of the TCR epitope. All three TCRs from patient Ob including that from the previously determined crystal structure show a counterclockwise rotation. Two of them are located near the N terminus of the peptide-binding cleft, whereas the third is near the center. These data are compatible with the hypothesis that the rotation of the TCRs may alter the downstream signaling.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563136 | PMC |
http://dx.doi.org/10.1073/pnas.0807338105 | DOI Listing |
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