Molecular mechanism of the allosteric enhancement of the umami taste sensation

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The fifth taste quality, umami, arises from binding of glutamate to the umami receptor T1R1/T1R3. The umami taste is enhanced several-fold upon addition of free nucleotides such as guanosine-5′-monophosphate (GMP) to glutamate-containing food. GMP may operate via binding to the ligand-binding domain of the T1R1 part of the umami receptor at an allosteric site. Using molecular dynamics simulations, we show that GMP can stabilize the closed (active) state of T1R1 by binding to the outer vestibule of the so-called Venus flytrap domain of the receptor. The transition between the closed and open conformations was accessed in the simulations. Using principal component analysis, we show that the dynamics of the Venus flytrap domain along the hinge-bending motion that activates signaling is dampened significantly upon binding of glutamate, and further slows down upon binding of GMP at an allosteric site, thus suggesting a molecular mechanism of cooperativity between GMP and glutamate.

Original languageEnglish
JournalF E B S Journal
Issue number17
Pages (from-to)3112-3120
Number of pages9
Publication statusPublished - 2012
Externally publishedYes

    Research areas

  • allosteric mechanism, GPCR, molecular dynamics, T1R1/T1R3, umami taste receptor

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