التفاصيل البيبلوغرافية
| العنوان: |
Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. |
| المؤلفون: |
Crump, Matthew P., Jiang-Hong Gong, Loetscher, Pius, Rajarathnam, Krishna, Amara, Ali, Arenzana-Seisdedos, Fernando, Virelizier, Jean-Louis, Baggiolini, Marco, Sykes, Brian D., Clark-Lewis, Ian |
| المصدر: |
EMBO Journal; 12/1/97, Vol. 16 Issue 23, p6996-7007, 12p |
| مصطلحات موضوعية: |
CHEMOKINES, G proteins, NUCLEAR magnetic resonance spectroscopy, PROTEIN synthesis, HIV, MONOMERS, BINDING sites |
| مستخلص: |
The three-dimensional structure of stromal cell-derived factor-1 (SDF-1) was determined by NMR spectroscopy. SDF-1 is a monomer with a disordered N-terminal region (residues 1–8), and differs from other chemokines in the packing of the hydrophobic core and surface charge distribution. Results with analogs showed that the N-terminal eight residues formed an important receptor binding site; however, only Lys-1 and Pro-2 were directly involved in receptor activation. Modification to Lys-1 and/or Pro-2 resulted in loss of activity, but generated potent SDF-1 antagonists. Residues 12–17 of the loop region, which we term the RFFESH motif, unlike the N-terminal region, were well defined in the SDF-1 structure. The RFFESH formed a receptor binding site, which we propose to be an important initial docking site of SDF-1 with its receptor. The ability of the SDF-1 analogs to block HIV-1 entry via CXCR4, which is a HIV-1 coreceptor for the virus in addition to being the receptor for SDF-1, correlated with their affinity for CXCR4. Activation of the receptor is not required for HIV-1 inhibition. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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