TY - JOUR
T1 - Structural determinants of CCR5 recognition and HIV-1 blockade in RANTES RID D-1688-2011
AU - Nardese, V
AU - Longhi, R
AU - Polo, S
AU - Sironi, F
AU - Arcelloni, C
AU - Paroni, R
AU - DeSantis, C
AU - Sarmientos, P
AU - RIZZI, Menico
AU - Bolognesi, M
AU - Pavone, V
AU - Lusso, P.
N1 - Funding Information:
We thank D.R. Littman for CCR5-transfected U87 cells (Ghost-CD4 cells), E.A. Berger for vaccinia virus vectors, E. Frittoli for technical assistance and S. Laus for editorial assistance. This work was supported by grants from the ISS AIDS Program, Rome, Italy.
PY - 2001
Y1 - 2001
N2 - Certain chemokines act as natural antagonists of human immunodeficiency virus (HIV) by blocking key viral coreceptors, such as CCR5 and CXCR4, on the surface of susceptible cells. Elucidating the structural determinants of the receptor-binding and HIV-inhibitory functions of these chemokines is essential for the rational design of derivative molecules of therapeutic value. Here, we identify the structural determinants of CCR5 recognition and antiviral activity of the CC chemokine RANTES, showing that critical residues form a solvent-exposed hydrophobic patch on the surface of the molecule. Moreover, we demonstrate that the biological function is critically dependent on dimerization, resulting in the exposure of a large (∼180 Å2), continuous hydrophobic surface. Relevant to the development of novel therapeutic approaches, we designed a retroinverted RANTES peptide mimetic that maintained both HIV- and chemotaxis-antagonistic functions.
AB - Certain chemokines act as natural antagonists of human immunodeficiency virus (HIV) by blocking key viral coreceptors, such as CCR5 and CXCR4, on the surface of susceptible cells. Elucidating the structural determinants of the receptor-binding and HIV-inhibitory functions of these chemokines is essential for the rational design of derivative molecules of therapeutic value. Here, we identify the structural determinants of CCR5 recognition and antiviral activity of the CC chemokine RANTES, showing that critical residues form a solvent-exposed hydrophobic patch on the surface of the molecule. Moreover, we demonstrate that the biological function is critically dependent on dimerization, resulting in the exposure of a large (∼180 Å2), continuous hydrophobic surface. Relevant to the development of novel therapeutic approaches, we designed a retroinverted RANTES peptide mimetic that maintained both HIV- and chemotaxis-antagonistic functions.
UR - https://iris.uniupo.it/handle/11579/6542
U2 - 10.1038/89653
DO - 10.1038/89653
M3 - Article
SN - 1072-8368
VL - 8
SP - 611
EP - 615
JO - Nature Structural Biology
JF - Nature Structural Biology
IS - 7
ER -
