2sdf: Difference between revisions
New page: left|200px<br /> <applet load="2sdf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2sdf" /> '''SOLUTION NMR STRUCTURE OF STROMAL CELL-DERI... |
No edit summary |
||
| Line 6: | Line 6: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known diseases associated with this structure: AIDS, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600835 600835]] | |||
==About this Structure== | ==About this Structure== | ||
| Line 26: | Line 29: | ||
[[Category: stromal cell-derived factor-1]] | [[Category: stromal cell-derived factor-1]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:38:03 2007'' | ||
