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PDBsum entry 4hcs
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Signaling protein
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PDB id
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4hcs
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References listed in PDB file
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Key reference
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Title
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Structural insight into the evolution of a new chemokine family from zebrafish.
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Authors
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D.Rajasekaran,
C.Fan,
W.Meng,
J.W.Pflugrath,
E.J.Lolis.
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Ref.
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Proteins, 2014,
82,
708-716.
[DOI no: ]
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PubMed id
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Abstract
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The mammalian chemokine family is segregated into four families - CC, CXC, CX3C,
and XC-based on the arrangement of cysteines and the corresponding disulfides.
Sequencing of the Danio rerio (zebrafish) genome has identified more than double
the amount of human chemokines with the absence of the CX3C family and the
presence of a new family, CX. The only other family with a single cysteine in
the N-terminal region is the XC family. Human lymphotactin (XCL1) has two
interconverting structures due to dynamic changes that occur in the protein.
Similar to an experiment with XCL1 that identified the two structural forms, we
probed for multiple forms of zCXL1 using heparin affinity. The results suggest
only a single form of CXL1 is present. We used sulfur-SAD phasing to determine
the three-dimensional structure CXL1. Zebrafish CXL1 (zCXL1) has three
disulfides that appear to be important for a stable structure. One disulfide is
common to all chemokines except those that belong to the XC family, another is
similar to a subset of CC chemokines containing three disulfides, but the third
disulfide is unique to the CX family. We analyzed the electrostatic potential of
the zCXL1 structure and identified the likely heparin-binding site for
glycosaminoglycans (GAGs). zCXL1 has a similar sequence identity with human CCL5
and CXCL12, but the structure is more related to CCL5. Our structural analysis
supports the phylogenetic and genomic studies on the evolution of the CXL
family. Proteins 2014; 82:708-716. © 2013 Wiley Periodicals, Inc.
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