TY - JOUR
T1 - Structure of the MORN4/Myo3a Tail Complex Reveals MORN Repeats as Protein Binding Modules
AU - Li, Jianchao
AU - Liu, Haiyang
AU - Raval, Manmeet H.
AU - Wan, Jun
AU - Yengo, Christopher M.
AU - Liu, Wei
AU - Zhang, Mingjie
N1 - Funding Information:
We thank the Shanghai Synchrotron Radiation Facility beamlines BL17U1 and BL19U1 for X-ray beam time. This work was supported by a grant from RGC of Hong Kong (16149516) to M.Z. grants from the National Natural Science Foundation of China (nos. 31670765 and 31870746 to W.L. and 31700673 to H.L.) and grants from Shenzhen Basic Research Grants (JCYJ20160229153100269 to M.Z. and JCYJ20170411090807530 to W.L.). M.Z. is a Kerry Holdings Professor in Science and a Senior Fellow of IAS at HKUST. J.L. H.L. and M.H.R. performed experiments. J.L. H.L. M.H.R. J.W. C.M.Y. W.L. and M.Z. analyzed data. J.L. H.L. W.L. and M.Z. designed the research. J.L. H.L. and M.Z. drafted the paper, and all authors commented on the paper. M.Z. coordinated the project. The authors declare no competing interests.
Funding Information:
We thank the Shanghai Synchrotron Radiation Facility beamlines BL17U1 and BL19U1 for X-ray beam time. This work was supported by a grant from RGC of Hong Kong ( 16149516 ) to M.Z., grants from the National Natural Science Foundation of China (nos. 31670765 and 31870746 to W.L. and 31700673 to H.L.) and grants from Shenzhen Basic Research Grants ( JCYJ20160229153100269 to M.Z. and JCYJ20170411090807530 to W.L.). M.Z. is a Kerry Holdings Professor in Science and a Senior Fellow of IAS at HKUST.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/9/3
Y1 - 2019/9/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2019.06.004
DO - 10.1016/j.str.2019.06.004
M3 - Article
C2 - 31279628
AN - SCOPUS:85071097169
SN - 0969-2126
VL - 27
SP - 1366-1374.e3
JO - Structure
JF - Structure
IS - 9
ER -