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 journalArticlepeer-review

23 Scopus citations

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

ASJC Scopus subject areas

  • General

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