The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly...The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor l-like （Eft1）, to pro- mote the release of eukaryotic initiation factor 6 （elF6） from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein （Sdolp） from yeast. Our data show that Sdolp interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2：2 dimer. Structural analysis indicates that Sdolp bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdolp on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdolp in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a con- formational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdolp, and Efllp, which interrogates the functional P-site to control the departure of the anti-association factor elF6.展开更多
文摘The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor l-like （Eft1）, to pro- mote the release of eukaryotic initiation factor 6 （elF6） from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein （Sdolp） from yeast. Our data show that Sdolp interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2：2 dimer. Structural analysis indicates that Sdolp bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdolp on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdolp in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a con- formational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdolp, and Efllp, which interrogates the functional P-site to control the departure of the anti-association factor elF6.
