PDBsum entry 3hr0

Transport protein

PDB id: 3hr0

Contents

Protein chains

250 a.a. *

Waters ×385

* Residue conservation analysis

PDB id:

3hr0

Name:

Transport protein

Title:

Crystal structure of homo sapiens conserved oligomeric golgi subunit 4

Structure:

Cog4. Chain: a, b. Fragment: residues 525-785. Synonym: conserved oligomeric golgi complex subunit 4, component of oligomeric golgi complex 4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cog4, cog4. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.196 R-free: 0.222

Authors:

B.C.Richardson,D.Ungar,A.Nakamura,P.D.Jeffrey,F.M.Hughson

Key ref:

B.C.Richardson et al. (2009). Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene. Proc Natl Acad Sci U S A, 106, 13329-13334. PubMed id: 19651599 DOI: 10.1073/pnas.0901966106

Date:

08-Jun-09 Release date: 21-Jul-09

Protein chains

Q9H9E3  (COG4_HUMAN) -  Conserved oligomeric Golgi complex subunit 4 from Homo sapiens

Seq: 785 a.a.

Struc: 250 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.0901966106

Proc Natl Acad Sci U S A 106:13329-13334 (2009)

PubMed id: 19651599

Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.

B.C.Richardson, R.D.Smith, D.Ungar, A.Nakamura, P.D.Jeffrey, V.V.Lupashin, F.M.Hughson.

ABSTRACT

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.

Selected figure(s)

Figure 1.
X-ray crystal structure of Cog4-(525–785). (A) H. sapiens Cog4, including residues 536–785. (B) Ionic interaction network centered around Arg 729.

Figure 4.
Structural alignment of Cog4-(525–785) to known COG, exocyst and Dsl1p subunits. (A) Shown are S. cerevisiae Tip20p (PDB ID 3FHN, residues 4–701 out of 701) (20), Cog2p (2JQQ, residues 109–262 out of 262) (14), Sec6p (2FJI, residues 411–805 out of 805) (18), Drosophila melanogaster Sec15 (2A2F, residues 382–699 out of 766) (19), S. cerevisiae Exo84p (2D2S, residues 525–753 out of 753) (15), and S. cerevisiae Exo70p (2PFV, residues 67–623 out of 623) (15–17). Pairwise alignment was performed with the program DaliLite (47) to match each of the other structures to Cog4-(525–785). The DaliLite Z scores for the alignments shown were 12.3 (Cog4-Tip20p), 3.8 (Cog4-Cog2p), 13.1 (Cog4-Sec6p), 10.1 (Cog4-Sec15), 6.2 (Cog4-Exo84p), and 8.0 (Cog4-Exo70p). (B) Cog4- (525–785) superimposed on proteins containing similar domains C, D, and E. (C) Stereoview of E domains, aligned using DaliLite and with the N terminus of each domain indicated by a red sphere. Included, in addition to the structures cited above, are the E domains of the cargo-binding domain of S. cerevisiae Myo2p (2F6H) (33) and the Dsl1p complex subunit Dsl1p (Y. Ren, P.D.J., and F.M.H., personal communication). No significant alignment was discernable for domain E of Tip20p.

Figures were selected by an automated process.