3N1E

Vps54 C-terminal domain

Summary for 3N1E

• Entry DOI: 10.2210/pdb3n1e/pdb
• Related: 2a2f 2fji 2pfv 3fhn 3hr0 3N1B
• Descriptor: Vacuolar protein sorting-associated protein 54, GLYCEROL, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: spinal muscular atrophy, vesicle trafficking, golgi apparatus, tethering complex, garp., transport protein
• Biological source: Mus musculus (mouse)
• Cellular location: Golgi apparatus, trans-Golgi network : Q5SPW0
• Total number of polymer chains: 2
• Total formula weight: 33019.63

Authors

Perez-Victoria, F.J.,Abascal-Palacios, G.,Tascon, I.,Kajava, A.,Pioro, E.P.,Bonifacino, J.S.,Hierro, A. (deposition date: 2010-05-15, release date: 2010-07-14, Last modification date: 2024-02-21)

Primary citation

Perez-Victoria, F.J.,Abascal-Palacios, G.,Tascon, I.,Kajava, A.,Magadan, J.G.,Pioro, E.P.,Bonifacino, J.S.,Hierro, A.
Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex.
Proc.Natl.Acad.Sci.USA, 107:12860-12865, 2010

PubMed Abstract: The multisubunit Golgi-associated retrograde protein (GARP) complex is required for tethering and fusion of endosome-derived transport vesicles to the trans-Golgi network. Mutation of leucine-967 to glutamine in the Vps54 subunit of GARP is responsible for spinal muscular atrophy in the wobbler mouse, an animal model of amyotrophic lateral sclerosis. The crystal structure at 1.7 A resolution of the mouse Vps54 C-terminal fragment harboring leucine-967, in conjunction with comparative sequence analysis, reveals that Vps54 has a continuous alpha-helical bundle organization similar to that of other multisubunit tethering complexes. The structure shows that leucine-967 is buried within the alpha-helical bundle through predominantly hydrophobic interactions that are critical for domain stability and folding in vitro. Mutation of this residue to glutamine does not prevent integration of Vps54 into the GARP complex but greatly reduces the half-life and levels of the protein in vivo. Severely reduced levels of mutant Vps54 and, consequently, of the whole GARP complex underlie the phenotype of the wobbler mouse.

PubMed: 20615984
DOI: 10.1073/pnas.1004756107

Experimental method

X-RAY DIFFRACTION (1.702 Å)