Polymorphic structural features of modelled HLA-DQ molecules segregate according to susceptibility or resistance to IDDM
Φόρτωση...
Ημερομηνία
Συγγραφείς
Routsias, J.
Papadopoulos, G. K.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Diabetologia
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The structural features of HLA-DQ alleles which are susceptible and resistant to insulin-dependent diabetes mellitus (IDDM) have been examined using a model of their three-dimensional structure obtained by energy minimisation, based on the published structure of HLA-DR1. The model shows DQ molecules to have an overall shape nearly identical to that of DR molecules, but with significant differences in the fine structure: 1) the antigen-binding groove of DQ molecules has a polymorphic first pocket; this pocket can be either amphiphilic or hydrophilic, 2) The beta 49-56 dimerisation domain of DQ is polymorphic: hydrophobic, or amphiphilic, or hydrophilic and positively charged, leading to spontaneous or T-cell receptor-induced homodimer formation, or T-cell receptor-induced homodimer formation, or difficulty of the formation of such dimers, respectively; 3) a prominent Arg-Gly-Asp loop is formed by some DQ alleles (beta 167-169) and probably functions in cell adhesion. There are also small differences in the residues and sequences implicated in CD4 binding (mostly in DQ beta 134-148) but the significance of these differences cannot be evaluated at present. All seven DQ alleles which confer susceptibility to IDDM possess a hydrophilic first pocket in the antigen-binding groove, a hydrophobic or amphiphilic beta 49-56 dimerisation patch that allows for spontaneous or T-cell receptor-induced dimerisation, and the Arg-Gly-Asp loop. By contrast, in the protective alleles at least one of these three features is absent. This segregation of phenotypes according to susceptibility or resistance can well explain the model of tighter autoantigen binding by the protective alleles compared to the susceptible alleles, previously proposed for the pathogenesis of IDDM.
Περιγραφή
Λέξεις-κλειδιά
Alleles, Amino Acid Sequence, Antigen Presentation, Antigens, CD4/chemistry/genetics, Diabetes Mellitus, Type 1/*immunology, Disease Susceptibility, HLA-DQ Antigens/*chemistry/genetics, Humans, Models, Chemical, Molecular Sequence Data, Oligopeptides/chemistry/genetics, Polymorphism, Genetic, Protein Conformation
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/8582533
http://www.springerlink.com/content/w413845418121n4n/fulltext.pdf
http://www.springerlink.com/content/w413845418121n4n/fulltext.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής