Monocarboxylate Transporter: Difference between revisions
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Thyroid hormones are essential for metabolism and neurological development. A recent study by Bågenholm et al. (2025) presents the cryo-electron microscopy (cryo-EM) structure of human MCT10 (PDB ID: [[9hhq]]), providing the first atomic-level view of this specific transporter class. | Thyroid hormones are essential for metabolism and neurological development. A recent study by Bågenholm et al. (2025) presents the cryo-electron microscopy (cryo-EM) structure of human MCT10 (PDB ID: [[9hhq]]), providing the first atomic-level view of this specific transporter class. | ||
* '''Monocarboxylate transporter 1''' and '''Monocarboxylate transporter 2''' promote transport of lactate and pyruvate which are essential for cell metabolism<ref>PMID:33559958</ref>,<ref>PMID:9786900</ref> .<br /> | |||
* '''Monocarboxylate transporter 8''' transports thyroid hormone across cell membrane<ref>PMID:12871948</ref>.<br /> | |||
== Structural Architecture == | == Structural Architecture == | ||
The structure (PDB: [[ | The structure (PDB: [[9hhq]]) reveals the canonical '''Major Facilitator Superfamily (MFS) fold'''. | ||
* '''Topology:''' The protein comprises 12 transmembrane helices (TM1–TM12) arranged into two pseudo-symmetric bundles: the '''N-terminal bundle''' (TM1–TM6) and the '''C-terminal bundle''' (TM7–TM12). | * '''Topology:''' The protein comprises 12 transmembrane helices (TM1–TM12) arranged into two pseudo-symmetric bundles: the '''N-terminal bundle''' (TM1–TM6) and the '''C-terminal bundle''' (TM7–TM12). | ||
* '''Conformation:''' The transporter was captured in an '''inward-open state'''. In this configuration, the central cavity is accessible from the cytoplasm, while the extracellular gate remains closed. | * '''Conformation:''' The transporter was captured in an '''inward-open state'''. In this configuration, the central cavity is accessible from the cytoplasm, while the extracellular gate remains closed. | ||
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== Mechanism of Action == | == Mechanism of Action == | ||
MCT10 likely operates via a '''"rocker-switch" mechanism'''. Comparison with AlphaFold models suggests that the N- and C-terminal bundles move as rigid bodies to alternatingly expose the binding site. A distinct kink in '''TM1''' (residues Gln88 and Asn89) acts as a sensor, likely triggering the conformational switch upon substrate binding. | MCT10 likely operates via a '''"rocker-switch" mechanism'''. Comparison with AlphaFold models suggests that the N- and C-terminal bundles move as rigid bodies to alternatingly expose the binding site. A distinct kink in '''TM1''' (residues Gln88 and Asn89) acts as a sensor, likely triggering the conformational switch upon substrate binding. | ||
== 3D sructures of monocarboxylate transporter == | |||
[[Monocarboxylate transporter 3D structures]] | |||
== References == | == References == | ||
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'''BI3323-Aug2025''' | '''BI3323-Aug2025''' | ||
[[Category:Topic Page]] | |||
