Profilin binds proline-rich ligands in two distinct amide backbone orientations.
The actin regulatory protein profilin is targeted to specific cellular regions through interactions with highly proline-rich motifs embedded within its binding partners. New X-ray crystallographic results demonstrate that profilin, like SH3 domains, can bind proline-rich ligands in two distinct amide backbone orientations. By further analogy with SH3 domains, these data suggest that non-proline residues in profilin ligands may dictate the polarity and register of binding, and the detailed organization of the assemblies involving profilin. This degeneracy may be a general feature of modules that bind proline-rich ligands, including WW and EVH1 domains, and has implications for the assembly and activity of macromolecular complexes involved in signaling and the regulation of the actin cytoskeleton.
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
N M
NM
Mahoney
D A
DA
Rozwarski
E
E
Fedorov
A A
AA
Fedorov
S C
SC
Almo
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000737:chemistry; D003285:Contractile Proteins; D006801:Humans; D007700:Kinetics; D008840:Microfilament Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D051304:Profilins; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D003285:Contractile Proteins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; D051304:Profilins; D011392:Proline