Sequence-specific dynamics modulate recognition specificity in WW domains.
The current canon attributes the binding specificity of protein-recognition motifs to distinctive chemical moieties in their constituent amino acid sequences. However, we show for a WW domain that the sequence crucial for specificity is an intrinsically flexible loop that partially rigidifies upon ligand docking. A single-residue deletion in this loop simultaneously reduces loop flexibility and ligand binding affinity. These results suggest that sequences of recognition motifs may reflect natural selection of not only chemical properties but also dynamic modes that augment specificity.
Peng
Tao
T
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 USA.
Zintsmaster
John S
JS
Namanja
Andrew T
AT
Peng
Jeffrey W
JW
D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D050505:Mutant Proteins / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009587:Nitrogen Isotopes; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013696:Temperature; D013816:Thermodynamics; D017186:Titrimetry; D020666:ras-GRF1 / Q000378:metabolism
D001059:Apoproteins; D050505:Mutant Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009587:Nitrogen Isotopes; D020666:ras-GRF1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase