Structural diversity of heparan sulfate binding domains in chemokines.
Heparan sulfate (HS) molecules are ubiquitous in animal tissues where they function as ligands that are dramatically involved in the regulation of the proteins they bind. Of these, chemokines are a family of small proteins with many biological functions. Their well-conserved monomeric structure can associate in various oligomeric forms especially in the presence of HS. Application of protein surface analysis and energy calculations to all known chemokine structures leads to the proposal that four different binding modes are created by the folding and oligomerization of these proteins. So, based on the present state of our knowledge, four different clusters of amino acids should be involved in the recognition process. Our results help to rationalize how unique sequences of HS specifically bind any given chemokine. The conclusions open the route for a rational design of compounds of therapeutical interest that could influence chemokine activity.
Lortat-Jacob
Hugues
H
Institut de Biologie Structurale, Centre National de la Recherche Scientifique-Commissariat à l'Energie Atomique-Université Joseph Fourier, Laboratoire de Biophysique Moléculaire, 41 Rue Horowitz, 38027 Grenoble Cedex 01, France.
Grosdidier
Aurélien
A
Imberty
Anne
A
D000595:Amino Acid Sequence; D001665:Binding Sites; D018925:Chemokines / Q000737:chemistry* / Q000378:metabolism*; D019992:Databases as Topic; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D015203:Reproducibility of Results; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software
D018925:Chemokines; D006497:Heparan Sulfate