Structural basis for the interaction of human herpesvirus 6B tetrameric glycoprotein complex with the cellular receptor, human CD134

PLoS Pathogens
Mitsuhiro NishimuraYasuko Mori

Abstract

A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD  = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 anti...Continue Reading

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Citations

Jul 25, 2021·International Journal of Molecular Sciences·Daniel G SausenRonen Borenstein

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Methods Mentioned

BETA
surface plasmon resonance
chip
enzyme-linked immunosorbent assay
ELISA
X-ray
electron microscopy
size exclusion column chromatography
size-exclusion column chromatography
size-exclusion
gel filtration

Software Mentioned

Phenix
cryoSPARC
BIAevaluation
MODEL
SWISS
refine
GCTF
. phaser
RELION
UCSF Chimera

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