Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission.
Membrane fusion and fission underlie two limiting steps of enveloped virus replication cycle: access to the interior of the host-cell (entry) and dissemination of viral progeny after replication (budding), respectively. These dynamic processes proceed mediated by specialized proteins that disrupt and bend the lipid bilayer organization transiently and locally. We introduced Wimley-White membrane-water partitioning free energies of the amino acids as an algorithm for predicting functional domains that may transmit protein conformational energy into membranes. It was found that many viral products possess unusually extended, aromatic-rich pre-transmembrane stretches predicted to stably reside at the membrane interface. Here, we review structure-function studies, as well as data reported on the interaction of representative peptides with model membranes, all of which sustain a functional role for these domains in viral fusion and fission. Since pre-transmembrane sequences also constitute antigenic determinants in a membrane-bound state, we also describe some recent results on their recognition and blocking at membrane interface by neutralizing antibodies.
Lorizate
Maier
M
Unidad de Biofísica CSIC-UPV/EHU, Universidad del País Vasco, Aptdo. 644, Bilbao, Spain.
Huarte
Nerea
N
Sáez-Cirión
Asier
A
Nieva
José L
JL
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008561:Membrane Fusion / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D014760:Viral Fusion Proteins; C514787:gp41 protein, Human immunodeficiency virus 1