9I59

RVFV GnH complexed with RVFV-379 Fab

Summary for 9I59

• Entry DOI: 10.2210/pdb9i59/pdb
• Descriptor: Envelopment polyprotein, Heavy chain of Fab, Light chain of Fab, ... (6 entities in total)
• Functional Keywords: rvfv glycoprotein fab complex, viral protein
• Biological source: Rift Valley fever virus; More
• Total number of polymer chains: 6
• Total formula weight: 172197.94

Authors

Paesen, G.C.,Bowden, T.A. (deposition date: 2025-01-27, release date: 2025-11-26, Last modification date: 2026-03-04)

Primary citation

Paesen, G.C.,Chapman, N.S.,Westover, J.B.,McMillen, C.M.,Kuzmina, N.A.,Dews, E.A.,Myers, L.,Stass, R.,Montgomery, J.M.,Bukreyev, A.,Hartman, A.L.,Gowen, B.B.,Crowe Jr., J.E.,Bowden, T.A.
Structural basis for recognition of Rift Valley fever virus Gn protein by a human neutralizing monoclonal antibody with a kappa light chain.
Plos Pathog., 22:e1013926-e1013926, 2026

PubMed Abstract: Rift Valley fever virus (RVFV) poses a continued threat to human health and animal husbandry. Two neutralizing and protective human monoclonal antibodies (mAbs), RVFV-268 and RVFV-379, exhibit similar affinities and epitope footprints on the Gn glycoprotein component of the RVFV Gn-Gc capsomeric lattice. Here, we define fine details of the biophysical determinants of Gn recognition used by RVFV human monoclonal antibodies through studying an antibody encoded by a set of recombined genes not previously identified in RVFV antibodies. We find that RVFV-379 exhibits a larger footprint than that observed for RVFV-268 and other antibodies targeting the same region, which involves major contributions of both the light and heavy chains. RVFV-379 also uses an oblique angle of approach towards the virion surface that contrasts with the perpendicular angle of engagement observed for some other potently neutralizing human mAbs. Further, consistent with amino acid sequence variation within and proximal to the RVFV-379 epitope, in vitro neutralization screening reveals a limited degree of neutralization breadth across prevalent RVFV strains, suggesting that RVFV has fewer functional constraints at this region of the virus envelope. By dissecting the molecular determinants of mAb recognition of Gn, this integrated analysis refines strategies needed for the rational design of vaccines that can elicit a potent and species-wide protective antibody immune response to this important re-emerging pathogen.

PubMed: 41701720
DOI: 10.1371/journal.ppat.1013926

Experimental method

X-RAY DIFFRACTION (2.09 Å)