Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues.

MBio
Kevin R McCarthyLindsey R Robinson-McCarthy

Abstract

EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying selection and its fusogenic activity has been maintained for over 40 million years. We determined the structure of the RBD of human EnvP(b)1, which defines structural similarities with extant leukemia viruses, despite little sequence conservation. This structure highlights a common scaffold from which novel receptor binding specificities likely evolved. The evolutionary plasticity of this domain may underlie the diversity of related Envs in circulating viruses.IMPORTANCE Organisms can access genetic and functional novelty by capturing viral elements within their gen...Continue Reading

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Datasets Mentioned

BETA
AGTM010332352.1
AGTM011595709.1
AGTM011264183.1
AGTM010685344
AGTM012840819.1

Methods Mentioned

BETA
glycosylation
transfection
gel filtration

Software Mentioned

PHENIX
ImageJ
RESOLVE
MLV
MolProbity
Dali
BLAST
PyMol
Phyre2
GenScript

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