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Structure-based classification defines the discrete conformational classes adopted by the arenaviral GP1

DOI: 10.1128/JVI.01048-18 DOI Help

Authors: Rhys Pryce (Wellcome Centre for Human Genetics, University of Oxford) , Weng M. Ng (Wellcome Centre for Human Genetics, University of Oxford) , Antra Zeltina (Wellcome Centre for Human Genetics, University of Oxford) , Yasunori Watanabe (Wellcome Centre for Human Genetics, University of Oxford; University of Southampton) , Kamel El Omari (Diamond Light Source) , Armin Wagner (Diamond Light Source) , Thomas A. Bowden (Wellcome Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 14744

Open Access Open Access

Abstract: The emergence of Old and New World arenaviruses from rodent reservoirs persistently threatens human health. The GP1 subunit of the envelope-displayed arenaviral glycoprotein spike complex, GPC, mediates host-cell recognition and is an important determinant of cross-species transmission. Previous structural analyses of Old World arenaviral GP1 glycoproteins, alone and in complex with a cognate GP2 subunit, have revealed that GP1 adopts two distinct conformational states, distinguished by differences in orientation of helical regions of the molecule. Here, through comparative study of the GP1 glycoprotein architectures of Old World Loei River virus and New World Whitewater Arroyo virus, we show that these rearrangements are restricted to Old World arenaviruses and are not solely induced by the pH change that is associated with virus endosomal trafficking. Our structure-based phylogenetic analysis of arenaviral GP1s provides a blueprint for understanding the discrete structural classes adopted by these therapeutically important targets.

Journal Keywords: arenavirus; glycoprotein; structure; X-ray crystallography; host-cell entry

Diamond Keywords: Viruses

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I23-Long wavelength MX

Added On: 16/10/2018 12:06


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)