PMC:4504005 / 19246-20276 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4504005","sourcedb":"PMC","sourceid":"4504005","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4504005","text":"RAMPs may confer selectivity by providing distinct contacts to the peptides, altering CLR conformation, or a combination of the two. Superposition of the CGRPmut- and AM-bound structures indicated that the RAMPs augment the peptide-binding site pocket with distinct residues from their α2-α3 loop and α2 (Figure 6A). RAMP1 W84 in the α2-α3 loop makes hydrophobic contact with the CGRPmut F37 phenyl ring. This contact would be lost in RAMP2, which has the smaller F111 at the equivalent position. RAMP2 E101 on α2 hydrogen bonds with AM K46 and Y52. The equivalent RAMP1 W74 cannot make these contacts. Two other peptide-proximal RAMP positions differ: RAMP1 F83/RAMP2 G110 on the α2-α3 loop and RAMP1 A70/RAMP2 R97 on α2 (Figure 6B). The F83/G110 position is close to CLR loop 4 and the R119 side chain that has different conformations in the two structures. RAMP2 R97, which participates in the hydrogen bond network near AM Y52, would sterically clash with a Trp at position 111. The small A70 in RAMP1 avoids a clash with W84.","tracks":[]}