Crystal structures of Uso1 membrane tether reveal an alternative conformation in the globular head domain.

Scientific Reports
Yoonyoung HeoHyung Ho Lee

Abstract

Membrane tethers play a critical role in organizing the complex molecular architecture of eukaryotic cells. Uso1 (yeast homolog of human p115) is essential for tethering in vesicle transport from ER to Golgi and interacts with Ypt1 GTPase. The N-terminal globular head domain of Uso1 is responsible for Ypt1 binding; however, the mechanism of tethering between ER transport vesicles and Golgi is unknown. Here, we determined two crystal structures for the Uso1 N-terminal head domain in two alternative conformations. The head domain of Uso1 exists as a monomer, as confirmed using size-exclusion chromatography coupled to multi-angle light scattering and analytical gel filtration. Although Uso1 consists of a right-handed α-solenoid, like that in mammalian homologs, the overall conformations of both Uso1 structures were not similar to previously known p115 structures, suggesting that it adopts alternative conformations. We found that the N- and C-terminal regions of the Uso1 head domain are connected by a long flexible linker, which may mediate conformational changes. To analyse the role of the alternative conformations of Uso1, we performed molecular docking of Uso1 with Ypt1, followed by a structural comparison. Taken together, we hy...Continue Reading

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Methods Mentioned

BETA
GTPases
size-exclusion
light scattering
electron microscopy
gel filtration
immunoprecipitation
size exclusion chromatography
gel-filtration
static light-scattering

Software Mentioned

COOT
ClustalW
PyMOL
HYDROPRO
DynDom
PHENIX
ASTRA
HKL2000
PyMOL Molecular Graphics System
HADDOCK

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