5NSJ

GP1 receptor-binding domain from Whitewater Arroyo mammarenavirus

Summary for 5NSJ

• Entry DOI: 10.2210/pdb5nsj/pdb
• Descriptor: Pre-glycoprotein polyprotein GP complex, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: viral glycoprotein, receptor binding domain, viral protein
• Biological source: Whitewater Arroyo mammarenavirus (WWAV)
• Cellular location: Stable signal peptide: Virion membrane ; Multi-pass membrane protein . Glycoprotein G1: Virion membrane ; Peripheral membrane protein . Glycoprotein G2: Virion membrane ; Single-pass membrane protein : Q911P0
• Total number of polymer chains: 2
• Total formula weight: 40271.52

Authors

Shimon, A.,Shani, O.,Diskin, R. (deposition date: 2017-04-26, release date: 2017-08-02, Last modification date: 2024-11-20)

Primary citation

Shimon, A.,Shani, O.,Diskin, R.
Structural Basis for Receptor Selectivity by the Whitewater Arroyo Mammarenavirus.
J. Mol. Biol., 429:2825-2839, 2017

PubMed Abstract: Whitewater Arroyo virus belongs to the "New World" group of mammarenaviruses that reside in rodent reservoirs and are prevalent in North and South Americas. Clades B and A/B of New World mammarenaviruses use transferrin receptor 1 (TfR1) for entry. While all of these viruses use rodent-derived TfR1 orthologs, some can also use the human-TfR1 and thereby infect humans. Although we have structural information for TfR1 recognition by pathogenic virus, we do not know what the structural differences are between the receptor-binding domains of pathogenic and non-pathogenic viruses that allow some but not all viruses to utilize the human receptor for entry. The poor understanding of the molecular determinants of mammarenavirus host range, and thus pathogenicity, is partly due to the low sequence similarity between the receptor-binding domains from these viruses and the limited available structural information that preclude the use of modeling approaches. Here we present the first crystal structure of a receptor-binding domain of a non-pathogenic clade A/B mammarenavirus. This structure reveals the magnitude of structural differences within the receptor-binding domains of TfR1-tropic viruses. Our structural and sequence analyses indicate that the same structural incompatibilities with the human receptor equally affect both pathogenic and non-pathogenic mammarenaviruses. Non-pathogenic viruses do not have specific structural elements that prevent them from using the human receptor. Instead, the ability to utilize the human receptor directly depends on the extent of weak interactions throughout the receptor-binding site that in some viruses are sufficiently strong to overcome the structural incompatibilities.

PubMed: 28736175
DOI: 10.1016/j.jmb.2017.07.011

Experimental method

X-RAY DIFFRACTION (2.249 Å)