3N1B: C-terminal domain of Vps54 subunit of the GARP complex

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.
PDB ID: 3N1BDownload
MMDB ID: 83368
PDB Deposition Date: 2010/5/15
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.398  Å
Source Organism:
Similar Structures:
Biological Unit for 3N1B: monomeric; determined by author
Molecular Components in 3N1B
Label Count Molecule
Protein (1 molecule)
Vacuolar Protein Sorting-associated Protein 54(Gene symbol: Vps54)
Molecule annotation
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Citing MMDB