Structure of the MORN4/Myo3a Tail Complex Reveals MORN Repeats as Protein Binding Modules

Jianchao Li; Haiyang Liu; Manmeet H Raval; Jun Wan; Christopher M Yengo; Wei Liu; Mingjie Zhang

doi:10.1016/j.str.2019.06.004

Structure of the MORN4/Myo3a Tail Complex Reveals MORN Repeats as Protein Binding Modules

Structure. 2019 Sep 3;27(9):1366-1374.e3. doi: 10.1016/j.str.2019.06.004. Epub 2019 Jul 3.

Authors

Jianchao Li¹, Haiyang Liu², Manmeet H Raval³, Jun Wan², Christopher M Yengo³, Wei Liu⁴, Mingjie Zhang⁵

Affiliations

¹ Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China.
² Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
³ Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
⁴ Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China. Electronic address: liuwei@sphmc.org.
⁵ Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: mzhang@ust.hk.

PMID: 31279628
DOI: 10.1016/j.str.2019.06.004

Abstract

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.

Keywords: MORN repeats; cargo recognition; myosin 3a; protein binding; tandem repeat proteins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
COS Cells
Chlorocebus aethiops
Crystallography, X-Ray
Male
Membrane Proteins / chemistry*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Models, Molecular
Myosin Heavy Chains / chemistry*
Myosin Heavy Chains / metabolism*
Protein Binding
Protein Conformation, beta-Strand
Protein Domains
Protein Folding
Tandem Repeat Sequences*

Substances

Membrane Proteins
Myosin Heavy Chains