protein
| RAB27A by its Slp N terminal domain |
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MYO5A by its C terminal region |
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in melanocytes, MYO5A tail interacts with its cargo-binding protein melanophilin (MLPH), which associates with melanosome via RAB27A |
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RAB27A is required for actin-based melanosome transport in mammalian skin melanocytes through its interaction with a specific effector MLPH |
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MLPH is the adapter protein that links RAB27A-melanosomes to MYO5A |
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MLPH-dependent changes in MYO5a depend on a positively charged cluster of amino acids in the actin binding domain of MLPH |
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RAB27A mutant (Q78L) is unable to localize on mature melanosomes and its inhibitory activity on melanosome transport is completely dependent on its binding to the RAB27A effector MLPH |
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MLPH/globular tail domain-binding domain (GTBD) is able to bind to the GTD of MYO5A in preactivated state and allosterically inhibits the binding of globular tail domain (GTD) to the head, thus inducing the extended conformation and activating the motor function of MYO5A |
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MLPH interaction with RAB27A is important for MLPH stability and melanosome transport |