Different stereochemical requirements for CXCR4 binding and signaling functions as revealed by an anti-HIV, D-amino acid-containing SMM-chemokine ligand.
Human immunodeficiency virus type 1 (HIV-1) uses a chemokine receptor, usually CXCR4 or CCR5, for entry into the target cells. Here, we used a chemical biology approach to demonstrate that binding and signaling domains in CXCR4 are possibly distinct and separate, as the new analogue, D(1-10)-vMIP-II-(9-68)-SDF-1alpha (RCP222), could not activate CXCR4 despite the fact that its binding activity was comparable to that of stromal cell-derived factor (SDF)-1alpha, the only natural ligand of CXCR4.
Dong
Chang-Zhi
CZ
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Kumar
Santosh
S
Choi
Won-Tak
WT
Madani
Navid
N
Tian
Shaomin
S
An
Jing
J
Sodroski
Joseph G
JG
Huang
Ziwei
Z
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054377:Chemokine CXCL12; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011869:Radioligand Assay; D019718:Receptors, CXCR4 / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D000596:Amino Acids; D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C507628:D(1-10)-vMIP-II-(9-68)-SDF-1alpha; D008024:Ligands; D019718:Receptors, CXCR4; C108059:vMIP-II; D002118:Calcium