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

Elongin is a heterotrimeric transcription elongation factor composed of sub units 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 in teracts with both elongin A and elongin B, as well as with the von Hippel-L indau tumor suppressor protein VHL. To investigate the corresponding intera ctions in yeast, we have utilized NMR spectroscopy combined with ultracentr ifugal sedimentation experiments to examine complexes of yeast elongin C (E lc1) with yeast elongin A (Ela1) and two peptides from homologous regions o f Ela1 and human VHL, Elc1 alone is a homotetramer composed of subunits wit h a structured N-terminal region and a dynamically unstable C-terminal regi on, 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 regi on of Elc1 into two regular helical structures and dissociates Elc1 into ho modimers. Moreover, analysis of the complex of Elc1 with the full Elc1-inte raction domain of Ela1 reveals that the Elc1 homodimer is dissociated to pr eferentially form an Ela1/Elc1 heterodimer, Thus, elongin C is found to oli gomerize in solution and to undergo significant structural rearrangements u pon binding of two different partner proteins. These results suggest a stru ctural basis for the interaction of an F-box-containing protein with a SKP1 homologue and the modulation of this interaction by the tumor suppressor V HL.