Peptide interactions stabilize and restructure human papillomavirus type 16 E6 to interact with p53.
Human papillomavirus type 16 (HPV-16) E6 (16E6) binds the E3 ubiquitin ligase E6AP and p53, thereby targeting degradation of p53 (M. Scheffner, B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley, Cell 63:1129-1136, 1990). Here we show that minimal 16E6-binding LXXLL peptides reshape 16E6 to confer p53 interaction and stabilize 16E6 in vivo but that degradation of p53 by 16E6 requires E6AP expression. These experiments establish a general mechanism for how papillomavirus E6 binding to LXXLL peptides reshapes E6 to then act as an adapter molecule.
Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Tina
T
Ansari
Nicole
N
Brimer
Scott B
SB
Vande Pol
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D052162:Human papillomavirus 16 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
C405928:CDK5RAP3 protein, human; D018797:Cell Cycle Proteins; C068651:E6 protein, Human papillomavirus type 16; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases