3hr0 | pdb_00003hr0
Crystal structure of Homo sapiens Conserved Oligomeric Golgi subunit 4
Structural highlights
Disease[COG4_HUMAN] Defects in COG4 are the cause of congenital disorder of glycosylation type 2J (CDG2J) [MIM:613489]. It is a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.[1] [2] Function[COG4_HUMAN] Required for normal Golgi function. Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.,Richardson BC, Smith RD, Ungar D, Nakamura A, Jeffrey PD, Lupashin VV, Hughson FM Proc Natl Acad Sci U S A. 2009 Jul 27. PMID:19651599[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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