Immunoglobulin Structure
The crystal framework and additionally revealed that the FSH/FSHR state-of-the-art models good dimer making use of the outside body off LRRs 2-4 throughout the hFSHR. cuatro ) did not change the dimerization of your hFSHR conveyed from inside the heterologous mobile products, although not. 217 The amazingly construction of one’s TSHR during the complex that have an excellent TSHR antibody don’t tell you one dimers. 216
Since the rely part is actually shed regarding a couple of ECD amazingly structures, there is nothing known in the the contribution on the complete conformation out-of the ECD and/or receptors. The newest finding that deposits step 1-268 of hFSHR (the newest fragment used in the new crystal build) attach hFSH with high attraction means that the fresh new hinge region of this new hFSHR is not working in binding. Concurrently, plenty of research-designed and of course-occurring mutations of one’s LHR show that the brand new hinge region of the fresh new hLHR isn’t essential brand new higher-attraction joining out of hLH or hCG. 211 However, the brand new large level of conservation of a few hinge part deposits when you look at the the newest glycoprotein hormonal receptor nearest and dearest ( Fig. 2.4 ) implies that this area takes on an important role various other elements out of receptor www.datingmentor.org/pl/kobiety-wybor-randki function for example activation (handled after from the text). An extremely saved Tyr within this area ( Fig. dos.4 ) try proven to be sulfated regarding the mobile epidermis TSHR and you can mutation from the Tyr impairs TSH binding and you will activation. 218 Sulfation of one’s similar Tyr about LHR otherwise FSHR wasn’t showed, but mutations of deposit from the gonadotropin receptors along with affect hormonal joining and you will activation. ? 218
The serpentine domain of the gonadotropin receptors is characterized by the canonical GPCR structure containing seven transmembrane (TM) segments joined by three alternating intracellular and extracellular loops ( Fig. 2.4 ). The amino acid sequences of this region of the hLHR and hFSHR are 72% identical ( Fig. 2.4 ). A three dimensional structure of the transmembrane domain of the gonadotropin receptors is lacking but the three dimensional structure of several other GPCRs with short extracellular domains have now been solved 213 (also see ) and the transmembrane domain of the gonadotropin receptors is likely to be very similar. Transmembrane domain residues that are highly conserved among the rodhopsin/?2-adrenergic receptor-like subfamily of GPCRs are also highlighted in Figure 2.4 .
27% identity, Fig. 2.4 ). An intracellular cysteine residue present in the juxtamembrane region of the C-terminal tail of the rodhopsin/?2-adrenergic receptor-like subfamily of GPCRs is, however, among the most highly conserved residues of this subfamily of GPCRs and all members of this subfamily examined to date have been shown to be palmitoylated at this site. This cysteine is towards the C-terminal end of a cytoplasmic helical segment of other GPCRs that is referred to as helix 8 ( ) and the palmitate present at this highly conserved position is thought to be embedded in the membrane. The LHR is unusual in having two adjacent cysteines in this position ( Fig. 2.4 ). Although the palmitoylation of the hLHR has not been studied, the mature form of the rLHR expressed in 293 cells, has been shown to be palmitoylated at both of these residues. 211 The equivalent cysteine in the hFSHR is also palmitoylated. 219
The hinge region
A separately encoded ‘hinge’ region is inserted between the CH1 and CH 2 domains. Portions of the hinge regions of two human IgG1 antibodies can be seen in Figure 3 and 4 . In the human and murine IgG1 subclasses, the initial part of the hinge region supplies the half-cysteine residue which forms the interchain disulfide bond with the L chain (see Figure 4 ). Its half-cystine counterpart in the L chain occupies the C-terminal location in a ? chain and the penultimate position in a ? chain. Disulfide bonds linking the two heavy chains are found in a relatively rigid ‘core’ segment (Cys-Pro-Pro-Cys-Pro) of the hinge region. Segments flanking this core section are responsible for the flexibility suggested by the name ‘hinge’. Papain hydrolyzes peptide bonds among residues 6–10 of the upper flexible segment (‘proximal hinge’) between the H–H and the H–L interchain disulfide bonds to produce Fabs. Pepsin cleaves the lower flexible segment (‘distal hinge’) after the disulfide bonds to release a (Fab?)2 fragment.