title: Structural basis of PSGL-1 binding to ERM proteins.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1), an adhesion molecule with O-glycosylated extracellular sialomucins, is involved in leukocyte inflammatory responses. On activation, ezrin-radixin-moesin (ERM) proteins mediate the redistribution of PSGL-1 on polarized cell surfaces to facilitate binding to target molecules. ERM proteins recognize a short binding motif, Motif-1, conserved in cytoplasmic tails of adhesion molecules, whereas PSGL-1 lacks Motif-1 residues important for binding to ERM proteins. The crystal structure of the complex between the radixin FERM domain and a PSGL-1 juxtamembrane peptide reveals that the peptide binds the groove of FERM subdomain C by forming a beta-strand associated with strand beta5C, followed by a loop flipped out towards the solvent. The Motif-1 3(10) helix present in the FERM-ICAM-2 complex is absent in PSGL-1 given the absence of a critical Motif-1 alanine residue, and PSGL-1 reduces its contact area with subdomain C. Non-conserved positions are occupied by large residues Met9 and His8, which stabilize peptide conformation and enhance groove binding. Non-conserved residues play an important role in compensating for loss of binding energy resulting from the absence of conserved residues important for binding.
authors: Structural Biology Laboratory, Nara Institute of Science and Technology, Nara, Japan.
authors: Yumiko
authors: Y
authors: Takai
authors: Ken
authors: K
authors: Kitano
authors: Shin-ichi
authors: S
authors: Terawaki
authors: Ryoko
authors: R
authors: Maesaki
authors: Toshio
authors: T
authors: Hakoshima
mesh_terms: D000818:Animals; D001665:Binding Sites; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D025581:Neurofibromin 2 / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D025581:Neurofibromin 2; C084882:P-selectin ligand protein