3WNX

Crystal structure of ERGIC-53/MCFD2, Calcium/Man3-bound form

Summary for 3WNX

• Entry DOI: 10.2210/pdb3wnx/pdb
• Related: 1GV9 1R1Z 2VRG 3A4U 3LCP 3WHT 3WHU 4GKX 4GKY
• Related PRD ID: PRD_900111
• Descriptor: Protein ERGIC-53, Multiple coagulation factor deficiency protein 2, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose, ... (5 entities in total)
• Functional Keywords: beta-sandwich, ef-hand, cargo receptor, calcium binding, er, ergic, protein transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 39713.02

Authors

Satoh, T.,Suzuki, K.,Yamaguchi, T.,Kato, K. (deposition date: 2013-12-18, release date: 2014-01-15, Last modification date: 2024-11-13)

Primary citation

Satoh, T.,Suzuki, K.,Yamaguchi, T.,Kato, K.
Structural Basis for Disparate Sugar-Binding Specificities in the Homologous Cargo Receptors ERGIC-53 and VIP36
Plos One, 9:e87963-e87963, 2014

PubMed Abstract: ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. VIP36 specifically interacts with the α1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the α1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcα1-3 linkage formation without steric hindrance. Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex.

PubMed: 24498414
DOI: 10.1371/journal.pone.0087963

Experimental method

X-RAY DIFFRACTION (2.75 Å)