Binding of elongin A or a von Hippel-Lindau peptide stabilizes the structure of yeast elongin C

Maria Victoria Botuyan, Christopher M. Koth, Georges Mer, Avi Chakrabartty, Joan W. Conaway, Ronald C. Conaway, Aled M. Edwards, Cheryl H. Arrowsmith, Walter J. Chazin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Elongin is a heterotrimeric transcription elongation factor composed of subunits A, B, and C in mammals. Elongin A and C are F-box-containing and SKP1 homologue proteins, respectively, and are therefore of interest for their potential roles in cell cycle-dependent proteolysis. Mammalian elongin C interacts with both elongin A and elongin B, as well as with the yon Hippel-Lindau tumor suppressor protein VHL. To investigate the corresponding interactions in yeast, we have utilized NMR spectroscopy combined with ultracentrifugal sedimentation experiments to examine complexes of yeast elongin C (Elc1) with yeast elongin A (Ela1) and two peptides from homologous regions of Ela1 and human VHL. Elc1 alone is a homotetramer composed of subunits with a structured N-terminal region and a dynamically unstable C- terminal region. Binding of a peptide fragment of the Elc1-interaction domain of Ela1 or with a homologous peptide from VHL promotes folding of the C- terminal region of Elc1 into two regular helical structures and dissociates Elc1 into homodimers. Moreover, analysis of the complex of Elc1 with the full Elc1-interaction domain of Ela1 reveals that the Elc1 homodimer is dissociated to preferentially form an Ela1/Elc1 heterodimer. Thus, elongin C is found to oligomerize in solution and to undergo significant structural rearrangements upon binding of two different partner proteins. These results suggest a structural basis for the interaction of an F-box-containing protein with a SKP1 homologue and the modulation of this interaction by the tumor suppressor VHL.

Original languageEnglish (US)
Pages (from-to)9033-9038
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number16
DOIs
StatePublished - Aug 3 1999
Externally publishedYes

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Yeasts
Peptides
Von Hippel-Lindau Tumor Suppressor Protein
F-Box Proteins
Peptide Elongation Factors
elongin
Peptide Fragments
Proteolysis
Mammals
Cell Cycle
Proteins
Transcription Factors
Magnetic Resonance Spectroscopy
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Binding of elongin A or a von Hippel-Lindau peptide stabilizes the structure of yeast elongin C. / Botuyan, Maria Victoria; Koth, Christopher M.; Mer, Georges; Chakrabartty, Avi; Conaway, Joan W.; Conaway, Ronald C.; Edwards, Aled M.; Arrowsmith, Cheryl H.; Chazin, Walter J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 16, 03.08.1999, p. 9033-9038.

Research output: Contribution to journalArticle

Botuyan, MV, Koth, CM, Mer, G, Chakrabartty, A, Conaway, JW, Conaway, RC, Edwards, AM, Arrowsmith, CH & Chazin, WJ 1999, 'Binding of elongin A or a von Hippel-Lindau peptide stabilizes the structure of yeast elongin C', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 16, pp. 9033-9038. https://doi.org/10.1073/pnas.96.16.9033
Botuyan, Maria Victoria ; Koth, Christopher M. ; Mer, Georges ; Chakrabartty, Avi ; Conaway, Joan W. ; Conaway, Ronald C. ; Edwards, Aled M. ; Arrowsmith, Cheryl H. ; Chazin, Walter J. / Binding of elongin A or a von Hippel-Lindau peptide stabilizes the structure of yeast elongin C. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 16. pp. 9033-9038.
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abstract = "Elongin is a heterotrimeric transcription elongation factor composed of subunits A, B, and C in mammals. Elongin A and C are F-box-containing and SKP1 homologue proteins, respectively, and are therefore of interest for their potential roles in cell cycle-dependent proteolysis. Mammalian elongin C interacts with both elongin A and elongin B, as well as with the yon Hippel-Lindau tumor suppressor protein VHL. To investigate the corresponding interactions in yeast, we have utilized NMR spectroscopy combined with ultracentrifugal sedimentation experiments to examine complexes of yeast elongin C (Elc1) with yeast elongin A (Ela1) and two peptides from homologous regions of Ela1 and human VHL. Elc1 alone is a homotetramer composed of subunits with a structured N-terminal region and a dynamically unstable C- terminal region. Binding of a peptide fragment of the Elc1-interaction domain of Ela1 or with a homologous peptide from VHL promotes folding of the C- terminal region of Elc1 into two regular helical structures and dissociates Elc1 into homodimers. Moreover, analysis of the complex of Elc1 with the full Elc1-interaction domain of Ela1 reveals that the Elc1 homodimer is dissociated to preferentially form an Ela1/Elc1 heterodimer. Thus, elongin C is found to oligomerize in solution and to undergo significant structural rearrangements upon binding of two different partner proteins. These results suggest a structural basis for the interaction of an F-box-containing protein with a SKP1 homologue and the modulation of this interaction by the tumor suppressor VHL.",
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AU - Koth, Christopher M.

AU - Mer, Georges

AU - Chakrabartty, Avi

AU - Conaway, Joan W.

AU - Conaway, Ronald C.

AU - Edwards, Aled M.

AU - Arrowsmith, Cheryl H.

AU - Chazin, Walter J.

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