Solution structure of human sorting nexin 22

Jikui Song, Kate Qin Zhao, Carrie L. Loushin Newman, Dmitriy A. Vinarov, John L. Markley
2007 Protein Science  
The sorting nexins (SNXs) constitute a large group of PX domain-containing proteins that play critical roles in protein trafficking. We report here the solution structure of human sorting nexin 22 (SNX22). Although SNX22 has <30% sequence identity with any PX domain protein of known structure, it was found to contain the a/b fold and compact structural core characteristic of PX domains. Analysis of the backbone dynamics of SNX22 by NMR relaxation measurements revealed that the two walls of the
more » ... igand binding cleft undergo internal motions: on the picosecond timescale for the b1/b2 loop and on the micro-to millisecond timescale for the loop between the polyproline motif and helix a2. Regions of the SNX22 structure that differ from those of other PX domains include the loop connecting strands b1 and b2 and the loop connecting helices a1 and a2, which appear to be more mobile than corresponding loops in other known structures. The interaction of dibutanoyl-phosphatidylinositol-3-phosphate (dibutanoyl-PtdIns(3)P) with SNX22 was investigated by an NMR titration experiment, which identified the binding site in a basic cleft and indicated that ligand binding leads only to a local structural rearrangement as has been found with other PX domains. Because motions in the loops are damped out when dibutanoyl-PtdIns(3)P binds, entropic effects could contribute to the lower affinity of SNX22 for this ligand compared to other PX domains.
doi:10.1110/ps.072752407 pmid:17400918 pmcid:PMC2206652 fatcat:5i35wn3tbndu3diflefxhjmgmi