Phylogenetic tree calculated using the neighbor-joining (NJ) method representing all human chemokines and their isoforms. The tree is based on the multiple sequence alignment. The three isoforms of CXCL12 (SDF-1α, β, and γ) are indicated at the uppermost portion of the figure.

Crystal structures of CXCL12. (a) Cartoon representation of the single protein chain of the asymmetric unit in the P3₂21 space group CXCL12 crystals. Chemokine structural elements are labeled. (b) The protein composition of the asymmetric unit in the P2₁2₁2₁ space group CXCL12 crystals. Ten monomers are arranged as an elongated decamer and form five CC-like dimers. (c) The semi-transparent surface representation of the asymmetric unit of the P3₂21 space group of CXCL12 and a symmetry mate forms a CXC dimer that interact through their α-helices and β-strand-1. (d) Semi-transparent surface of two representative chains in the decamer of CXCL12 which form a CC chemokine-like dimer and interact with their amino termini and 30’s loops. (e) CXC dimer of CXCL12 (upper panel) compared to CC dimer of CXCL12 (lower panel). Both dimers were aligned using only Chain A of each in the alignment algorithm.

Intersubunit contacts of CXCL12 dimers. (a) Arginine zipper motif forms the interactions in the amino terminal regions of the CC-like CXCL12 dimer. Cysteines are colored yellow, arginines from chains A and B are colored purple and red, respectively. (b) Crystallographic packing between CC-dimers. Cartoon representation with semi-transparent surface of two representative chains in the decamer of CXCL12 in between each CC chemokine-like dimer. (c) Overlay of the CC-like dimer of CXCL12 and the CC dimer of CCL5. Chain A from each dimer was aligned. Glutamic acid 15 from CXCL12 and isoleucine 15 from CCL5 are shown as sticks to indicate the 180° rotation of the carbon backbone.