Structural model of human alpha1-microglobulin: proposed scheme for the interaction with the Gla domain of anticoagulant protein C.
Alpha1-microglobulin (alpha1m) is a small glycoprotein with immunomodulatory properties. It is a member of the lipocalin family, a group of proteins that exhibit a well-conserved three-dimensional structure despite low sequence identity and that are known to bind small hydrophobic ligands. The types of ligands carried by alpha1m are still unknown, but it is known that this protein has yellow-brown chromophores attached to three lysines at position 92, 118 and 130. Alpha1m has one unpaired cysteine residue (Cys 34) that can form a disulphide bond with other proteins that also possess an exposed free unpaired cysteine. For instance, alpha1m interacts with the protein C (PC) Gla domain containing the Arg9Cys or Ser12Cys substitution. In order to gain insights about the alpha1m molecule and analyze the intriguing alpha1m-Gla domain interaction, it was decided to use bioinformatics. The three-dimensional structures of alpha1m and PC Gla domain were predicted. Alpha1m Cys 34 is solvent exposed and located near the entrance of the ligand-binding pocket. The chromophore-carrying lysines are found buried into the pocket, and the area around the entrance of this cavity displays about 10 positively charged residues. This electropositive region in alpha1m complements the essentially electronegative Gla domain and may play a role during intermolecular interactions. In addition, a few hydrophobic residues surround alpha1m Cys 34 and could be of importance during its interaction with macromolecular ligands.
Villoutreix
B O
BO
Department of Cell and Molecular Biology, Lund University, Sweden.
Akerström
B
B
Lindqvist
A
A
D000595:Amino Acid Sequence; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011486:Protein C / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014360:Trypsin Inhibitor, Kunitz Soybean
D008562:Membrane Glycoproteins; D011486:Protein C; C109148:SPINT2 protein, human; D014360:Trypsin Inhibitor, Kunitz Soybean