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.
Mahoney
N M
NM
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Rozwarski
D A
DA
Fedorov
E
E
Fedorov
A A
AA
Almo
S C
SC
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