4HSI: Glycoprotein B From Herpes Simplex Virus Type 1, A504p/r505g/q507g/n511g Mutant, Low-ph

Citation:
Abstract
Viral fusogens mediate the merger of the viral envelope and cellular membrane during viral entry. These proteins share little sequence similarity but all are thought to act by refolding through a series of conformational intermediates from the metastable prefusion form to the stable postfusion form. Crystal structures of both prefusion and postfusion forms have illuminated the conformational pathways of several viral fusogens. By contrast, only the structure of the postfusion form is available for glycoprotein B (gB), the conserved fusogen of herpesviruses. To gain insight into the nature of the fusogenic conformational changes in gB, we used several approaches aimed at engineering the prefusion form of the herpes simplex virus type 1 gB ectodomain, including modifications intended to stabilize the prefusion form and novel mutations aimed at destabilizing the postfusion form. We found that the postfusion conformation of gB is remarkably stable and resistant to perturbations. Several mutations successfully destabilized the gB trimer, identifying regions that are critical for the stability of the postfusion form. Yet, none of the constructs adopted the prefusion conformation. We propose that the soluble ectodomain of gB folds into the postfusion form without first adopting the prefusion intermediate. These results suggest that other regions of gB, including the transmembrane region and the cytoplasmic domain, may be necessary to establish and maintain the metastable prefusion conformation.
PDB ID: 4HSIDownload
MMDB ID: 108675
PDB Deposition Date: 2012/10/30
Updated in MMDB: 2013/05
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Similar Structures:
Biological Unit for 4HSI: trimeric; determined by author and by software (PISA)
Molecular Components in 4HSI
Label Count Molecule
Proteins (3 molecules)
3
Envelope Glycoprotein B
Molecule annotation
Chemicals (12 molecules)
1
6
2
3
3
3
* Click molecule labels to explore molecular sequence information.

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