3S6X

Structure of reovirus attachment protein sigma1 in complex with alpha-2,3-sialyllactose

Summary for 3S6X

• Entry DOI: 10.2210/pdb3s6x/pdb
• Related: 1KKE 2OJ5 3EOY 3S6Y 3S6Z
• Descriptor: Outer capsid protein sigma-1, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: triple beta-spiral, beta-barrel, beta-spiral repeat, greek key motif, trimer, viral attachment protein, sialic acid receptors junctional adhesion molecule a, viral capsid, viral protein
• Biological source: Reovirus type 3 (Mammalian orthoreovirus 3)
• Cellular location: Virion: P03528
• Total number of polymer chains: 3
• Total formula weight: 107982.99

Authors

Reiter, D.M.,Dermody, T.S.,Stehle, T. (deposition date: 2011-05-26, release date: 2011-11-23, Last modification date: 2024-02-28)

Primary citation

Reiter, D.M.,Frierson, J.M.,Halvorson, E.E.,Kobayashi, T.,Dermody, T.S.,Stehle, T.
Crystal structure of reovirus attachment protein sigma1 in complex with sialylated oligosaccharides
Plos Pathog., 7:e1002166-e1002166, 2011

PubMed Abstract: Many viruses attach to target cells by binding to cell-surface glycans. To gain a better understanding of strategies used by viruses to engage carbohydrate receptors, we determined the crystal structures of reovirus attachment protein σ1 in complex with α-2,3-sialyllactose, α-2,6-sialyllactose, and α-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structure of σ1 resembles an elongated, filamentous trimer. It contains a globular head featuring a compact β-barrel, and a fibrous extension formed by seven repeating units of a triple β-spiral that is interrupted near its midpoint by a short α-helical coiled coil. The carbohydrate-binding site is located between β-spiral repeats two and three, distal from the head. In all three complexes, the terminal sialic acid forms almost all of the contacts with σ1 in an identical manner, while the remaining components of the oligosaccharides make little or no contacts. We used this structural information to guide mutagenesis studies to identify residues in σ1 that functionally engage sialic acid by assessing hemagglutination capacity and growth in murine erythroleukemia cells, which require sialic acid binding for productive infection. Our studies using σ1 mutant viruses reveal that residues 198, 202, 203, 204, and 205 are required for functional binding to sialic acid by reovirus. These findings provide insight into mechanisms of reovirus attachment to cell-surface glycans and contribute to an understanding of carbohydrate binding by viruses. They also establish a filamentous, trimeric carbohydrate-binding module that could potentially be used to endow other trimeric proteins with carbohydrate-binding properties.

PubMed: 21829363
DOI: 10.1371/journal.ppat.1002166

Experimental method

X-RAY DIFFRACTION (2.25 Å)