Molecular mechanism of constitutively active Rab11A was revealed by crystal structure of Rab11A S20V

Jae Young Choi, Young Cheul Shin, Jong Hwan Yoon, Chang Min Kim, Jun Hyuck Lee, Ju-Hong Jeon, Hyun Ho Park

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Rab11A is a small GTP-binding protein involved in the regulation of vesicle trafficking during recycling of endosomes. Substitution of S20 to V (S20V) at Rab11A inhibits the GTP hydrolysis activity of Rab11A. This mutation is known to be constitutively in an active form. Here, we report the crystal structure of the human Rab11A S20V mutant form complexed with GTP at a resolution of 2.4 Å. Without adding any substrate, Rab11A contained non-hydrolyzed natural substrate GTP in the nucleotide binding pocket with Mg2+. In our observations, substituted V20 of Rab11A was found to interfere with proper localization of the water molecule, which mediated GTP hydrolysis, resulting in GTP being locked in an active form of Rab11A S20V.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalFEBS Letters
Volume590
Issue number6
DOIs
StatePublished - 1 Mar 2016

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Guanosine Triphosphate
Crystal structure
Hydrolysis
Endosomes
Substrates
GTP-Binding Proteins
Recycling
Substitution reactions
Nucleotides
Mutation
Molecules
Water

Keywords

  • Rab11
  • crystal structure
  • membrane trafficking
  • small G protein

Cite this

Choi, Jae Young ; Shin, Young Cheul ; Yoon, Jong Hwan ; Kim, Chang Min ; Lee, Jun Hyuck ; Jeon, Ju-Hong ; Park, Hyun Ho. / Molecular mechanism of constitutively active Rab11A was revealed by crystal structure of Rab11A S20V. In: FEBS Letters. 2016 ; Vol. 590, No. 6. pp. 819-827.
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abstract = "Rab11A is a small GTP-binding protein involved in the regulation of vesicle trafficking during recycling of endosomes. Substitution of S20 to V (S20V) at Rab11A inhibits the GTP hydrolysis activity of Rab11A. This mutation is known to be constitutively in an active form. Here, we report the crystal structure of the human Rab11A S20V mutant form complexed with GTP at a resolution of 2.4 {\AA}. Without adding any substrate, Rab11A contained non-hydrolyzed natural substrate GTP in the nucleotide binding pocket with Mg2+. In our observations, substituted V20 of Rab11A was found to interfere with proper localization of the water molecule, which mediated GTP hydrolysis, resulting in GTP being locked in an active form of Rab11A S20V.",
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Molecular mechanism of constitutively active Rab11A was revealed by crystal structure of Rab11A S20V. / Choi, Jae Young; Shin, Young Cheul; Yoon, Jong Hwan; Kim, Chang Min; Lee, Jun Hyuck; Jeon, Ju-Hong; Park, Hyun Ho.

In: FEBS Letters, Vol. 590, No. 6, 01.03.2016, p. 819-827.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Choi, Jae Young

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AU - Yoon, Jong Hwan

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AU - Lee, Jun Hyuck

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AB - Rab11A is a small GTP-binding protein involved in the regulation of vesicle trafficking during recycling of endosomes. Substitution of S20 to V (S20V) at Rab11A inhibits the GTP hydrolysis activity of Rab11A. This mutation is known to be constitutively in an active form. Here, we report the crystal structure of the human Rab11A S20V mutant form complexed with GTP at a resolution of 2.4 Å. Without adding any substrate, Rab11A contained non-hydrolyzed natural substrate GTP in the nucleotide binding pocket with Mg2+. In our observations, substituted V20 of Rab11A was found to interfere with proper localization of the water molecule, which mediated GTP hydrolysis, resulting in GTP being locked in an active form of Rab11A S20V.

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