title: Structural elements of the osteopontin SVVYGLR motif important for the interaction with alpha(4) integrins.
abstract: The osteopontin SVVYGLR motif binds the integrins alpha(4)beta(1) and alpha(9)beta(1). We show that alpha(4)beta(7) also interacts with this motif and that an SVVYGLR-OH peptide antagonises the alpha(4)beta(7) MAdCAM interaction. The important elements of this motif required to bind alpha(4)beta(1) and alpha(4)beta(7) were probed using a series of mutated peptides based around SVVYGLR. Leu167 is important for the interaction with alpha(4) integrins, as is the C-terminal carboxylic acid of Arg168 exposed by thrombin cleavage. The importance of the acidic group means that SVVYGLR has structural elements in common with other alpha(4) integrin-binding motifs and suggests why thrombin cleavage activates this motif.
authors.affiliation: Systems Research, GlaxoSmithKline Medicines Research Centre, Stevenage, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Green
authors.forename: S B
authors.initials: SB
authors.lastname: Ludbrook
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
authors.forename: C M
authors.initials: CM
authors.lastname: Horgan
authors.forename: S T
authors.initials: ST
authors.lastname: Barry
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D039441:Integrin alpha4; D053495:Osteopontin; D011487:Protein Conformation; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D039441:Integrin alpha4