Title : Comparison of
GFL-GFRalpha complexes: further evidence relating
GFL bend angle to RET signalling
Abstract :
- Glial cell line-derived neurotrophic factor ( GDNF ) activates the receptor tyrosine kinase RET by binding to the GDNF-family receptor alpha1 (GFRalpha1 ) and forming the GDNF ( 2 )- GFRalpha1 ( 2 )- RET ( 2 ) heterohexamer complex
- A previous crystal structure of the GDNF ( 2 )- GFRalpha1 ( 2 ) complex (PDB code 2v5e) suggested that differences in signalling in GDNF-family ligand ( GFL ) complexes might arise from differences in the bend angle between the two monomers in the GFL homodimer
- Here, a 2 .35 A resolution structure of the GDNF ( 2 )- GFRalpha1 ( 2 ) complex crystallized with new cell dimensions is reported
- The structure was refined to a final R factor of 2 2 .5% (R(free) = 28%)
- The structures of both biological tetrameric complexes in the asymmetric unit are very similar to 2v5e and different from the artemin- GFRalpha3 structure, even though there is a small change in the structure of the GDNF
- By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling
- Comparisons also suggest that the differences between artemin and GDNF arise from the increased curvature of the artemin ;fingers', which both increases the buried surface area in the monomer-monomer interface and changes the intermonomer bend angle
- From sequence comparison, it is suggested that neuturin (the second GFL ) adopts an artemin-like conformation, while persephin has a different conformation to the other three
Output (sent_index, trigger,
protein,
sugar,
site):
- 5. change, , structure of the GDNF, change, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):