2SDF

SOLUTION NMR STRUCTURE OF STROMAL CELL-DERIVED FACTOR-1 (SDF-1), 30 STRUCTURES

Summary for 2SDF

• Entry DOI: 10.2210/pdb2sdf/pdb
• Descriptor: STROMAL CELL-DERIVED FACTOR-1 (1 entity in total)
• Functional Keywords: cytokine, sdf-1, chemokines, stromal cell-derived factor-1, g-coupled receptors, protein synthesis, solution structure
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P48061
• Total number of polymer chains: 1
• Total formula weight: 7849.28

Authors

Crump, M.P.,Rajarathnam, K.,Clark-Lewis, I.,Sykes, B.D. (deposition date: 1998-03-07, release date: 1998-06-17, Last modification date: 2024-10-16)

Primary citation

Crump, M.P.,Gong, J.H.,Loetscher, P.,Rajarathnam, K.,Amara, A.,Arenzana-Seisdedos, F.,Virelizier, J.L.,Baggiolini, M.,Sykes, B.D.,Clark-Lewis, I.
Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1.
EMBO J., 16:6996-7007, 1997

PubMed Abstract: 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.

PubMed: 9384579
DOI: 10.1093/emboj/16.23.6996

Experimental method

SOLUTION NMR