6V3V

Assembly of VIQKI I456(beta-L-homoisoleucine)with human parainfluenza virus type 3 (HPIV3) fusion glycoprotein N-terminal heptad repeat domain

Summary for 6V3V

• Entry DOI: 10.2210/pdb6v3v/pdb
• Descriptor: Fusion glycoprotein F1 (3 entities in total)
• Functional Keywords: fusion glycoprotein, six-helix bundle, foldamer, viral protein
• Biological source: Human parainfluenza 3 virus (strain Wash/47885/57) (HPIV-3); More
• Total number of polymer chains: 6
• Total formula weight: 29596.19

Authors

Outlaw, V.K.,Gellman, S.H. (deposition date: 2019-11-26, release date: 2020-10-21, Last modification date: 2023-11-15)

Primary citation

Outlaw, V.K.,Kreitler, D.F.,Stelitano, D.,Porotto, M.,Moscona, A.,Gellman, S.H.
Effects of Single alpha-to-beta Residue Replacements on Recognition of an Extended Segment in a Viral Fusion Protein.
Acs Infect Dis., 6:2017-2022, 2020

PubMed Abstract: Partial replacement of α-amino acid residues with β-amino acid residues has been established as a strategy for preserving target-engagement by helix-forming polypeptides while altering other properties. The impact of β-residue incorporation within polypeptides that adopt less regular conformations, however, has received less attention. The C-terminal heptad repeat (HRC) domains of fusion glycoproteins from pathogenic paramyxoviruses contain a segment that must adopt an extended conformation in order to coassemble with the N-terminal heptad repeat (HRN) domain in the postfusion state and drive a merger of the viral envelope with a target cell membrane. Here, we examine the impact of single α-to-β substitutions within this extended N-terminal segment of an engineered HRC peptide designated VIQKI. Stabilities of hexameric coassemblies formed with the native human parainfluenza virus 3 (HPIV3) HRN have been evaluated, the structures of five coassemblies have been determined, and antiviral efficacies have been measured. Many sites within the extended segment show functional tolerance of α-to-β substitution. These results offer a basis for future development of paramyxovirus infection inhibitors with novel biological activity profiles, possibly including resistance to proteolysis.

PubMed: 32692914
DOI: 10.1021/acsinfecdis.0c00385

Experimental method

X-RAY DIFFRACTION (2.17 Å)