Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein

Hao Song1, Zhennan Zhao2, Yan Chai3

  • 1Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.

Cell
|May 14, 2019
PubMed

Insights

Chikungunya virus (CHIKV) uses the MXRA8 receptor for cell entry. Structural studies reveal MXRA8 binds CHIKV

Area of Science:

  • Virology and Structural Biology
  • Molecular mechanisms of viral entry

Background:

  • Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), cause significant global morbidity and economic burden due to rheumatic diseases.
  • MXRA8 has recently been identified as a critical cellular entry receptor for CHIKV.
  • Understanding the molecular interactions between CHIKV and MXRA8 is crucial for developing antiviral therapies.

Purpose of the Study:

  • To elucidate the structural basis of CHIKV binding to its receptor, MXRA8.
  • To provide atomic-level insights into the interaction interface for therapeutic target identification.

Main Methods:

  • X-ray crystallography was employed to determine the structures of mouse MXRA8, human MXRA8 complexed with CHIKV E protein, and CHIKV virus-like particles bound to human MXRA8.
  • Cryo-electron microscopy provided high-resolution structural data of the MXRA8-CHIKV complex.

Main Results:

  • MXRA8 possesses two Ig-like domains with distinct structural topologies.
  • The receptor binds within a 'canyon' formed by CHIKV E protein protomers on the virion surface.
  • Atomic interactions involve both MXRA8 domains and hinge region with CHIKV E1-E2 residues, and the stalk region is vital for viral entry.

Conclusions:

  • The detailed structural understanding of the MXRA8-CHIKV interaction provides a foundation for designing targeted antiviral strategies.
  • Identifying the critical role of the MXRA8 stalk region offers a new avenue for therapeutic intervention against CHIKV and related alphaviruses.

Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.7K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
19.7K
What are Viruses?00:50

What are Viruses?

Overview
127.9K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.3K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
16.7K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.5K