Details

Autor(en) / Beteiligte

• Luo, Zhaowen
• Zhou, Naiming
• Luo, Jiansong
• Hall, James W
• Huang, Ziwei

Titel

The Role of Positively Charged Residues in CXCR4 Recognition Probed with Synthetic Peptides

Ist Teil von

• Biochemical and biophysical research communications, 1999-10, Vol.263 (3), p.691-695

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1999

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• A high positive charge is the common characteristic shared by the β-sheet region of stromal cell-derived factor-1 (SDF-1) and CXCR4 antagonists such as ALX40-4C consisting of nine D-arginines. This raises the question that the positively charged residues may play a role in recognition of CXCR4. To test this hypothesis, two studies were carried out using synthetic peptides. In the first study, peptide analogs possessing amino acid sequences from both the N-terminus and the β-sheet region of SDF-1 were used as models to study the functional role of the β-sheet region of SDF-1. The attachment of positively charged residues to the N-terminal peptide sequence of SDF-1 was found to enhance the ability of the peptides in CXCR4 binding and inhibiting CXCR4-mediated T-tropic HIV-1 entry. In the second study, two peptides containing nine arginines and the N-terminal signal sequence of SDF-1 were used as models to study the receptor binding mechanism of CXCR4 antagonists of high positive charges such as ALX40-4C. One peptide did not show signaling activity as indicated by the lack of calcium influx while another peptide induced unusual calcium influx distinct from that induced by the SDF-1 N-terminal peptide. In addition, the signal induced by the SDF-1 N-terminal peptide was inhibited by ALX40-4C. Therefore, the first study provides experimental support for the role of the highly positive β-sheet region of SDF-1 in CXCR4 binding. The second study suggests that the binding site of ALX40-4C in CXCR4 may partially overlap with that of the SDF-1 N-terminal peptide. Both findings should be valuable for the design of SDF-1 agonists and antagonists.