2ETT

Solution Structure of Human Sorting Nexin 22 PX Domain

Summary for 2ETT

• Entry DOI: 10.2210/pdb2ett/pdb
• Descriptor: Sorting nexin-22 (1 entity in total)
• Functional Keywords: px domain, sorting nexin 22, bc019655, snx22_human, hs.157607, structural genomics, protein structure initiative, psi, center for eukaryotic structural genomics, cesg, protein transport
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): Q96L94
• Total number of polymer chains: 1
• Total formula weight: 15219.48

Authors

Song, J.,Zhao, Q.,Tyler, R.C.,Lee, M.S.,Newman, C.L.,Markley, J.L.,Center for Eukaryotic Structural Genomics (CESG) (deposition date: 2005-10-27, release date: 2005-11-15, Last modification date: 2024-05-22)

Primary citation

Song, J.,Zhao, K.Q.,Newman, C.L.,Vinarov, D.A.,Markley, J.L.
Solution structure of human sorting nexin 22.
Protein Sci., 16:807-814, 2007

PubMed Abstract: 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 alpha/beta 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 ligand binding cleft undergo internal motions: on the picosecond timescale for the beta1/beta2 loop and on the micro- to millisecond timescale for the loop between the polyproline motif and helix alpha2. Regions of the SNX22 structure that differ from those of other PX domains include the loop connecting strands beta1 and beta2 and the loop connecting helices alpha1 and alpha2, 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.

PubMed: 17400918
DOI: 10.1110/ps.072752407

Experimental method

SOLUTION NMR