1A15

SDF-1ALPHA

Summary for 1A15

• Entry DOI: 10.2210/pdb1a15/pdb
• Descriptor: STROMAL DERIVED FACTOR-1ALPHA, SULFATE ION (3 entities in total)
• Functional Keywords: chemokine, human stromal cell-derived factor-1alpha
• Cellular location: Secreted: P48061
• Total number of polymer chains: 2
• Total formula weight: 15708.57

Authors

Dealwis, C.G.,Fernandez, E.J.,Lolis, E. (deposition date: 1997-12-22, release date: 1998-08-12, Last modification date: 2024-10-23)

Primary citation

Dealwis, C.,Fernandez, E.J.,Thompson, D.A.,Simon, R.J.,Siani, M.A.,Lolis, E.
Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1alpha, a potent ligand for the HIV-1 "fusin" coreceptor.
Proc.Natl.Acad.Sci.USA, 95:6941-6946, 1998

PubMed Abstract: Stromal cell-derived factor-1alpha (SDF-1alpha ) is a member of the chemokine superfamily and functions as a growth factor and chemoattractant through activation of CXCR4/LESTR/Fusin, a G protein-coupled receptor. This receptor also functions as a coreceptor for T-tropic syncytium-inducing strains of HIV-1. SDF-1alpha antagonizes infectivity of these strains by competing with gp120 for binding to the receptor. The crystal structure of a variant SDF-1alpha ([N33A]SDF-1alpha ) prepared by total chemical synthesis has been refined to 2.2-A resolution. Although SDF-1alpha adopts a typical chemokine beta-beta-beta-alpha topology, the packing of the alpha-helix against the beta-sheet is strikingly different. Comparison of SDF-1alpha with other chemokine structures confirms the hypothesis that SDF-1alpha may be either an ancestral protein from which all other chemokines evolved or the chemokine that is the least divergent from a primordial chemokine. The structure of SDF-1alpha reveals a positively charged surface ideal for binding to the negatively charged extracellular loops of the CXCR4 HIV-1 coreceptor. This ionic complementarity is likely to promote the interaction of the mobile N-terminal segment of SDF-1alpha with interhelical sites of the receptor, resulting in a biological response.

PubMed: 9618518
DOI: 10.1073/pnas.95.12.6941

Experimental method

X-RAY DIFFRACTION (2.2 Å)