Biophysical characterization reveals structural disorder in the developmental transcriptional regulator LBH

Hassan Al-Ali, Megan E. Rieger, Kenneth L. Seldeen, Thomas K Harris, Amjad Farooq, Karoline Briegel

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Limb-bud and heart (LBH) is a key transcriptional regulator in vertebrates with pivotal roles in embryonic development and human disease. Herein, using a diverse array of biophysical techniques, we report the first structural characterization of LBH pertinent to its biological function. Our data reveal that LBH is structurally disordered with no discernable secondary or tertiary structure and exudes rod-like properties in solution. Consistent with these observations, we also demonstrate that LBH is conformationally flexible and thus may be capable of adapting distinct conformations under specific physiological contexts. We propose that LBH is a member of the intrinsically disordered protein (IDP) family, and that conformational plasticity may play a significant role in modulating LBH-dependent transcriptional processes.

Original languageEnglish
Pages (from-to)1104-1109
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
StatePublished - Jan 1 2010

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Limb Buds
Intrinsically Disordered Proteins
Embryonic Development
Plasticity
Conformations
Vertebrates

Keywords

  • Embryonic development
  • Intrinsically disordered proteins
  • LBH
  • Transcriptional regulation
  • Vertebrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

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AU - Al-Ali, Hassan

AU - Rieger, Megan E.

AU - Seldeen, Kenneth L.

AU - Harris, Thomas K

AU - Farooq, Amjad

AU - Briegel, Karoline

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N2 - Limb-bud and heart (LBH) is a key transcriptional regulator in vertebrates with pivotal roles in embryonic development and human disease. Herein, using a diverse array of biophysical techniques, we report the first structural characterization of LBH pertinent to its biological function. Our data reveal that LBH is structurally disordered with no discernable secondary or tertiary structure and exudes rod-like properties in solution. Consistent with these observations, we also demonstrate that LBH is conformationally flexible and thus may be capable of adapting distinct conformations under specific physiological contexts. We propose that LBH is a member of the intrinsically disordered protein (IDP) family, and that conformational plasticity may play a significant role in modulating LBH-dependent transcriptional processes.

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