Differential pairing of transmembrane domain GxxxG dimerization motifs defines two HLA-DR MHC class II conformers

Discovering immunoreceptor coupling and organization motifs

“…So far, two different TMD dimerization motifs have been studied, namely the GxxxG motif and the LZ motif ( 63 ). The GxxxG motif has been studied in the context of the glycophorin A function ( 64 , 65 ) but it also plays an important role in the dimerization and proper membrane localization of murine and human MHC class II proteins ( 66 , 67 ). The LZ motif has been extensively studied in the context of the EPO-R ( 68 ) and PDGFR ( 43 ).…”

Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis

“…Using the 11–5.2 monoclonal antibody (mAb), which exhibits selective binding to I-A k class II molecules, it was observed that the single GxxxG motif in the molecule’s β chain interacts with the N-terminal M1 GxxxG motif situated within the I-A k α chain . Furthermore, it was noted that the binding of the Tü36 mAb is specifically hindered by mutations in the M1 α chain GxxxG motif, highlighting potential structural and functional differences …”

“…37 Furthermore, it was noted that the binding of the Tu36 mAb is specifically hindered by mutations in the M1 α chain GxxxG motif, highlighting potential structural and functional differences. 38 A striking similarity between these segment and Alzheimer's Aβ peptide (UniProt accession ID of Amyloid Precursor protein (P05067)) is that both can form helical dimer in the presence of membrane mimicking detergent-micelle. 39,40 The hydrophobic environment of a lipid bilayer, which facilitates hydrogen bonding is likely to promote dimerization.…”