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

Botuyan MV, Koth CM, Mer G, Chakrabartty A, Conaway JW, Conaway RC, Edwards AM, Arrowsmith CH, Chazin WJ
Proc Natl Acad Sci U S A. 1999 96 (16): 9033-8

PMID: 10430890 · PMCID: PMC17727 · DOI:10.1073/pnas.96.16.9033

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 von 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.

MeSH Terms (24)

Amino Acid Sequence Animals Elongin Genes, Tumor Suppressor Humans Hydrogen Bonding Ligases Macromolecular Substances Mammals Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Proteins Protein Structure, Secondary Rats Recombinant Proteins Saccharomyces cerevisiae Sequence Alignment Sequence Homology, Amino Acid Transcription Factors Tumor Suppressor Proteins Ubiquitin-Protein Ligases Ultracentrifugation Von Hippel-Lindau Tumor Suppressor Protein

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