HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels.
The persistent infection of human glial cells with HIV-1 is characterized by prominent expression of the Nef protein. In order to evaluate the possible role of Nef in the development of HIV-1-associated neurological disorders, we compared Nef with known neuroactive proteins. We found that HIV Nef shares sequence and structural features with scorpion peptides known to interact with K+ channels. Sequence similarity encompasses two distinct regions of scorpion peptides. Based on crystallography data, both regions in scorpion peptides cooperate in forming a common domain stabilized by ion pairs between charged amino-acid residues. Recombinant Nef protein, as well as a synthetic part of a scorpion channel active peptide (M10), reversibly increased the total K+ current of chick dorsal root ganglions in patch-clamp experiments without killing the cells. These results indicate that a region conserved in HIV Nef and scorpion peptides concurs in both structure and electrophysiological activity and suggest that Nef, like scorpion peptides, may affect neuronal cell function.
Werner
T
T
GSF Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany.
Ferroni
S
S
Saermark
T
T
Brack-Werner
R
R
Banati
R B
RB
Mager
R
R
Steinaa
L
L
Kreutzberg
G W
GW
Erfle
V
V
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002460:Cell Line; D004594:Electrophysiology; D015693:Gene Products, nef / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D012604:Scorpion Venoms / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D009479:Neuropeptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D054311:nef Gene Products, Human Immunodeficiency Virus