Tandem repeats are basic building blocks for constructing proteins with diverse structures and functions. Compared with extensively studied α-helix-based tandem repeats such as ankyrin, tetratricopeptide, armadillo, and HEAT repeat proteins, relatively little is known about tandem repeat proteins formed by β hairpins. In this study, we discovered that the MORN repeats from MORN4 function as a protein binding module specifically recognizing a tail cargo binding region from Myo3a. The structure of the MORN4/Myo3a complex shows that MORN4 forms an extended single-layered β-sheet structure and uses a U-shaped groove to bind to the Myo3a tail with high affinity and specificity. Sequence and structural analyses further elucidated the unique sequence features for folding and target binding of MORN repeats. Our work establishes that the β-hairpin-based MORN repeats are protein-protein interaction modules. The crystal structure of MORN4/Myo3a complex reveals that MORN4 can use its highly conserved U-shaped groove to interact with Myo3a tail with high affinity and specificity and suggests that MORN repeats are versatile protein-protein interaction modules.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology