Peripherin-2: an intracellular analogy to viral fusion proteins.
The C-terminus of the intracellular retinal rod outer segment disk protein peripherin-2 binds to membranes, adopts a helical conformation, and promotes membrane fusion, which suggests an analogy to the structure and function of viral envelope fusion proteins. Nuclear magnetic resonance (NMR) data and fluorescence data show that a 63-residue polypeptide comprising the C-terminus of bovine peripherin-2 (R284-G346) binds to the membrane mimetic, dodecylphosphocholine micelles. High-resolution NMR studies reveal that although this C-terminal fragment is unstructured in solution, the same fragment adopts helical structure when bound to the micelles. The C-terminus may be a member of the class of intrinsically unstructured protein domains. Using methods developed for the G-protein coupled receptor rhodopsin, a model for the structure of the transmembrane domain of peripherin-2 was constructed. Previously published data showed that both peripherin-2 and viral fusion proteins are transmembrane proteins that promote membrane fusion and have a fusion peptide sequence within the protein that independently promotes membrane fusion. Furthermore, the fusion-active sequence of peripherin-2 exhibits a sequence motif that matches the viral fusion peptide of influenza hemagglutinin (HA). These observations collectively suggest that the mechanism of intracellular membrane fusion induced by peripherin-2 and the mechanism of enveloped viral fusion may have features in common.
Edrington
T C
TC
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269, USA.
Lapointe
R
R
Yeagle
P L
PL
Gretzula
C L
CL
Boesze-Battaglia
K
K
D020816:Amino Acid Motifs; D000818:Animals; D002417:Cattle; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008823:Micelles; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D064531:Peripherins; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008823:Micelles; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; D014760:Viral Fusion Proteins; D010767:Phosphorylcholine; C028810:dodecylphosphocholine