5MV8

Structure of human Myosin 7b C-terminal MyTH4-FERM domain in complex with harmonin-a PDZ3 domain

Summary for 5MV8

• Entry DOI: 10.2210/pdb5mv8/pdb
• Descriptor: Unconventional myosin-VIIb, cDNA FLJ51329, highly similar to Harmonin, GLYCEROL, ... (5 entities in total)
• Functional Keywords: myosin, motor protein, harmonin, myosin tail, pdz
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytoskeleton : Q6PIF6
• Total number of polymer chains: 2
• Total formula weight: 75597.74

Authors

Yu, I.,Sourigues, Y.,Titus, M.A.,Houdusse, A. (deposition date: 2017-01-16, release date: 2017-07-05, Last modification date: 2024-05-08)

Primary citation

Yu, I.M.,Planelles-Herrero, V.J.,Sourigues, Y.,Moussaoui, D.,Sirkia, H.,Kikuti, C.,Stroebel, D.,Titus, M.A.,Houdusse, A.
Myosin 7 and its adaptors link cadherins to actin.
Nat Commun, 8:15864-15864, 2017

PubMed Abstract: Cadherin linkages between adjacent stereocilia and microvilli are essential for mechanotransduction and maintaining their organization. They are anchored to actin through interaction of their cytoplasmic domains with related tripartite complexes consisting of a class VII myosin and adaptor proteins: Myo7a/SANS/Harmonin in stereocilia and Myo7b/ANKS4B/Harmonin in microvilli. Here, we determine high-resolution structures of Myo7a and Myo7b C-terminal MyTH4-FERM domain (MF2) and unveil how they recognize harmonin using a novel binding mode. Systematic definition of interactions between domains of the tripartite complex elucidates how the complex assembles and prevents possible self-association of harmonin-a. Several Myo7a deafness mutants that map to the surface of MF2 disrupt harmonin binding, revealing the molecular basis for how they impact the formation of the tripartite complex and disrupt mechanotransduction. Our results also suggest how switching between different harmonin isoforms can regulate the formation of networks with Myo7a motors and coordinate force sensing in stereocilia.

PubMed: 28660889
DOI: 10.1038/ncomms15864

Experimental method

X-RAY DIFFRACTION (1.88 Å)