4YMR

Crystal structure of the domain swapped PXB/TPR domain of mouse SNX21

Summary for 4YMR

• Entry DOI: 10.2210/pdb4ymr/pdb
• Descriptor: Protein Snx21 (2 entities in total)
• Functional Keywords: tetratricopeptide repeat endosome trafficking, protein transport
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : Q3UR97
• Total number of polymer chains: 2
• Total formula weight: 32062.75

Authors

Collins, B.C.,Teasdale, R.D.,Clairfeuille, T. (deposition date: 2015-03-07, release date: 2015-04-29, Last modification date: 2024-02-28)

Primary citation

Clairfeuille, T.,Norwood, S.J.,Qi, X.,Teasdale, R.D.,Collins, B.M.
Structure and Membrane Binding Properties of the Endosomal Tetratricopeptide Repeat (TPR) Domain-containing Sorting Nexins SNX20 and SNX21.
J.Biol.Chem., 290:14504-14517, 2015

PubMed 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 α-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.

PubMed: 25882846
DOI: 10.1074/jbc.M115.650598

Experimental method

X-RAY DIFFRACTION (2.4 Å)