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.
Graduate School of Science and Engineering, Ehime University, Matsuyama, Japan.
Takeshi
T
Tenno
Kenichiro
K
Fujiwara
Hidehito
H
Tochio
Kazuhiro
K
Iwai
E Hayato
EH
Morita
Hidenori
H
Hayashi
Shigeo
S
Murata
Hidekazu
H
Hiroaki
Mamoru
M
Sato
Keiji
K
Tanaka
Masahiro
M
Shirakawa
D008239:Lysine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D025821:Polyubiquitin / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D025821:Polyubiquitin; D008239:Lysine