Functionally distinct monomers and trimers produced by a viral oncoprotein.
While the process of homo-oligomer formation and disassembly into subunits represents a common strategy to regulate protein activity, reports of proteins in which the subunit and homo-oligomer perform independent functions are scarce. Tumorigenesis induced by the adenovirus E4-ORF1 oncoprotein depends on its binding to a select group of cellular PDZ proteins, including MUPP1, MAGI-1, ZO-2 and Dlg1. We report here that in cells E4-ORF1 exists as both a monomer and trimer and that monomers specifically bind and sequester MUPP1, MAGI-1 and ZO-2 within insoluble complexes whereas trimers specifically bind Dlg1 and promote its translocation to the plasma membrane. This work exposes a novel strategy wherein the oligomerization state of a protein not only determines the capacity to bind separate related targets but also couples the interactions to different functional consequences.
Chung
S-H
SH
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Weiss
R S
RS
Frese
K K
KK
Prasad
B V V
BV
Javier
R T
RT
D017504:Adenovirus E4 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary / Q000502:physiology; D011755:Pyrophosphatases / Q000737:chemistry / Q000235:genetics