5XBF

Crystal Structure of Myo7b C-terminal MyTH4-FERM in complex with USH1C PDZ3

Summary for 5XBF

• Entry DOI: 10.2210/pdb5xbf/pdb
• Descriptor: Unconventional myosin-VIIb, Harmonin, GLYCEROL, ... (6 entities in total)
• Functional Keywords: protein complex, molecular motor, motor protein, protein transport-structural protein complex, protein transport/structural protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytoskeleton : Q6PIF6; Cytoplasm, cytosol : Q9Y6N9
• Total number of polymer chains: 2
• Total formula weight: 73771.46

Authors

Li, J.,He, Y.,Weck, W.L.,Lu, Q.,Tyska, M.J.,Zhang, M. (deposition date: 2017-03-17, release date: 2017-05-17, Last modification date: 2024-03-27)

Primary citation

Li, J.,He, Y.,Weck, M.L.,Lu, Q.,Tyska, M.J.,Zhang, M.
Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins.
Proc. Natl. Acad. Sci. U.S.A., 114:E3776-E3785, 2017

PubMed Abstract: Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.

PubMed: 28439001
DOI: 10.1073/pnas.1702251114

Experimental method

X-RAY DIFFRACTION (1.802 Å)