Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains.
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves as a signalling function that controls a wide variety of cellular processes. To date, two major forms of polyubiquitin chain have been functionally characterized, in which the isopeptide bond linkages involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to target proteins for degradation by the proteasome, whereas Lys63-linked polyubiquitination has been linked to numerous cellular events that do not rely on degradative signalling via the proteasome. Apparently linkage-specific conformations of polyubiquitin chains are important for these cellular functions, but the structural bases distinguishing Lys48- and Lys63-linked chains remain elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48-linked chains, Lys63-linked chains are elongated molecules with no stable non-covalent intersubunit interfaces and thus adopt a radically different conformation from that of Lys48-linked chains.
Tenno
Takeshi
T
Graduate School of Science and Engineering, Ehime University, Matsuyama, Japan.
Fujiwara
Kenichiro
K
Tochio
Hidehito
H
Iwai
Kazuhiro
K
Morita
E Hayato
EH
Hayashi
Hidenori
H
Murata
Shigeo
S
Hiroaki
Hidekazu
H
Sato
Mamoru
M
Tanaka
Keiji
K
Shirakawa
Masahiro
M
D008239:Lysine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D025821:Polyubiquitin / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D025821:Polyubiquitin; D008239:Lysine