Structural Basis for a Human Glycosylation Disorder Caused by Mutation of the COG4 Gene
The proper glycosylation of proteins trafficking through the Golgi apparatus depends upon the conserved oligomeric Golgi (COG) complex. Defects in COG can cause fatal congenital disorders of glycosylation (CDGs) in humans. The recent discovery of a form of CDG, caused in part by a COG4 missense mutation changing Arg 729 to Trp, prompted us to determine the 1.9 A crystal structure of a Cog4 C-terminal fragment. Arg 729 is found to occupy a key position at the center of a salt bridge network, thereby stabilizing Cog4's small C-terminal domain. Studies in HeLa cells reveal that this C-terminal domain, while not needed for the incorporation of Cog4 into COG complexes, is essential for the proper glycosylation of cell surface proteins. We also find that Cog4 bears a strong structural resemblance to exocyst and Dsl1p complex subunits. These complexes and others have been proposed to function by mediating the initial tethering between transport vesicles and their membrane targets; the emerging structural similarities provide strong evidence of a common evolutionary origin and may reflect shared mechanisms of action.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 980500
- Report Number(s):
- BNL-93418-2010-JA; TRN: US201015%%1885
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, Issue 32
- Country of Publication:
- United States
- Language:
- English
Similar Records
Structure of a C-terminal fragment of its Vps53 subunit suggests similarity of Golgi-associated retrograde protein (GARP) complex to a family of tethering complexes
Structural Characterization of Tip20p and Dsl1p, Subunits of the Dsl1p Vesicle Tethering Complex
Related Subjects
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
COMPLEXES
CRYSTAL STRUCTURE
DEFECTS
FUNCTIONS
GENES
GOLGI COMPLEXES
HELA CELLS
HUMAN POPULATIONS
MEMBRANES
MUTATIONS
ORIGIN
PROTEINS
SALTS
SURFACES
TARGETS
TRANSPORT
national synchrotron light source