Dataset Information


Structure and Membrane Binding Properties of the Endosomal Tetratricopeptide Repeat (TPR) Domain-containing Sorting Nexins SNX20 and SNX21.

ABSTRACT: Sorting nexins (SNX) orchestrate membrane trafficking and signaling events required for the proper distribution of proteins within the endosomal network. Their phox homology (PX) domain acts as a phosphoinositide (PI) recognition module that targets them to specific endocytic membrane domains. The modularity of SNX proteins confers a wide variety of functions from signaling to membrane deformation and cargo binding, and many SNXs are crucial modulators of endosome dynamics and are involved in a myriad of physiological and pathological processes such as neurodegenerative diseases, cancer, and inflammation. Here, we have studied the poorly characterized SNX20 and its paralogue SNX21, which contain an N-terminal PX domain and a C-terminal PX-associated B (PXB) domain of unknown function. The two proteins share similar PI-binding properties and are recruited to early endosomal compartments by their PX domain. The crystal structure of the SNX21 PXB domain reveals a tetratricopeptide repeat (TPR)-fold, a module that typically binds short peptide motifs, with three TPR ?-helical repeats. However, the C-terminal capping helix adopts a highly unusual and potentially self-inhibitory topology. SAXS solution structures of SNX20 and SNX21 show that these proteins adopt a compact globular architecture, and membrane interaction analyses indicate the presence of overlapping PI-binding sites that may regulate their intracellular localization. This study provides the first structural analysis of this poorly characterized subfamily of SNX proteins, highlighting a likely role as endosome-associated scaffolds.

SUBMITTER: Clairfeuille T 

PROVIDER: S-EPMC4505518 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC6140323 | BioStudies
2001-01-01 | S-EPMC1222026 | BioStudies
2020-01-01 | S-EPMC7083883 | BioStudies
1000-01-01 | S-EPMC3941054 | BioStudies
2013-01-01 | S-EPMC3581954 | BioStudies
1000-01-01 | S-EPMC2776105 | BioStudies
2007-01-01 | S-EPMC1949010 | BioStudies
2017-01-01 | S-EPMC5348129 | BioStudies
2011-01-01 | S-EPMC3093529 | BioStudies
2020-01-01 | S-EPMC7082075 | BioStudies