Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide

Maria Victoria Botuyan, Georges Mer, Gwan Su Yi, Christopher M. Koth, David A. Case, Aled M. Edwards, Walter J. Chazin, Cheryl H. Arrowsmith

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Elongin is a transcription elongation factor that stimulates the rate of elongation by suppressing transient pausing by RNA polymerase II at many sites along the DNA. It is heterotrimeric in mammals, consisting of elongins A, B and C subunits, and bears overall similarity to a class of E3 ubiquitin ligases known as SCF (Skp1-Cdc53 (cullin)-F-box) complexes. A subcomplex of elongins B and C is a target for negative regulation by the von Hippel-Lindau (VHL) tumor-suppressor protein. Elongin C from Saccharomyces cerevisiae, Elc1, exhibits high sequence similarity to mammalian elongin C. Using NMR spectroscopy we have determined the three-dimensional structure of Elc1 in complex with a human VHL peptide, VHL(157-171), representing the major Elc1 binding site. The bound VHL peptide is entirely helical. Elc1 utilizes two C-terminal helices and an intervening loop to form a binding groove that fits VHL(157-171). Chemical shift perturbation and dynamics analyses reveal that a global conformational change accompanies Elc1/VHL(157-171) complex formation. Moreover, the disappearance of conformational exchange phenomena on the microsecond to millisecond time scale within Eld upon VHL peptide binding suggests a role for slow internal motions in ligand recognition.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalJournal of Molecular Biology
Volume312
Issue number1
DOIs
StatePublished - Sep 7 2001
Externally publishedYes

Fingerprint

Yeasts
Peptides
Von Hippel-Lindau Tumor Suppressor Protein
Cullin Proteins
Peptide Elongation Factors
Ubiquitin-Protein Ligases
RNA Polymerase II
Saccharomyces cerevisiae
Mammals
Transcription Factors
Magnetic Resonance Spectroscopy
Binding Sites
Ligands
DNA
elongin

Keywords

  • Conformational change
  • Elongin
  • Ligand recognition
  • NMR solution structure
  • Von Hippel-Lindau

ASJC Scopus subject areas

  • Virology

Cite this

Botuyan, M. V., Mer, G., Yi, G. S., Koth, C. M., Case, D. A., Edwards, A. M., ... Arrowsmith, C. H. (2001). Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide. Journal of Molecular Biology, 312(1), 177-186. https://doi.org/10.1006/jmbi.2001.4938

Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide. / Botuyan, Maria Victoria; Mer, Georges; Yi, Gwan Su; Koth, Christopher M.; Case, David A.; Edwards, Aled M.; Chazin, Walter J.; Arrowsmith, Cheryl H.

In: Journal of Molecular Biology, Vol. 312, No. 1, 07.09.2001, p. 177-186.

Research output: Contribution to journalArticle

Botuyan, MV, Mer, G, Yi, GS, Koth, CM, Case, DA, Edwards, AM, Chazin, WJ & Arrowsmith, CH 2001, 'Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide', Journal of Molecular Biology, vol. 312, no. 1, pp. 177-186. https://doi.org/10.1006/jmbi.2001.4938
Botuyan, Maria Victoria ; Mer, Georges ; Yi, Gwan Su ; Koth, Christopher M. ; Case, David A. ; Edwards, Aled M. ; Chazin, Walter J. ; Arrowsmith, Cheryl H. / Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide. In: Journal of Molecular Biology. 2001 ; Vol. 312, No. 1. pp. 177-186.
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