SPECTROSCOPIC STUDY OF AN HIV-1 CAPSID PROTEIN MAJOR HOMOLOGY REGION PEPTIDE ANALOG

The capsid (CA) domain of retroviral Gag proteins posseses one subdoma in, the major homology region (MHR), which is conserved among nearly a ll avian and mammalian retroviruses. While it is known that the mutage nesis of residues in the MHR mill impair virus infectivity, the precis e structure and function of the MHR is not known. In order to obtain f urther information on the MHR, we have examined the structure of a syn thetic peptide encompassing the MHR of human immunodeficiency virus ty pe I (HIV-1) CA protein. Multiple sequence alignment and secondary str ucture prediction indicate that the peptide could form 50% alpha-helix and 10% beta-sheet. In addition, circular dichroism studies indicate that, in the presence of 50% trifluoroethanol (TFE), the peptide adopt s an alpha-helical structure over half of its length. Further analysis by proton nuclear magnetic resonance spectroscopy suggests that the C -terminal portion of the MHR forms a helix in aqueous solution. Upon t he addition of TFE, the position of the helix remains nearly constant, but the magnitude of the changes in H-alpha chemical shifts of the re sidues indicate a more stable helix. These results suggest that a heli cal C-terminus of retroviral MHRs may be integral to the function of t his region.