共 38 条
Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy
被引:94
作者:
Hsu, Shang-Te Danny
Fucini, Paola
Cabrita, Lisa D.
Launay, Helene
Dobson, Christopher M.
Christodoulou, John
机构:
[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England
[2] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[3] Univ Frankfurt, Inst Organ Chem & Chem Biol, D-60438 Frankfurt, Germany
来源:
基金:
英国医学研究理事会;
英国惠康基金;
关键词:
cotranslational folding;
D O I:
10.1073/pnas.0704664104
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Protein folding in living cells is inherently coupled to protein synthesis and chain elongation. There is considerable evidence that some nascent chains fold into their native structures in a cotranslational manner before release from the ribosome, but, despite its importance, a detailed description of such a process at the atomic level remains elusive. We show here at a residue-specific level that a nascent protein chain can reach its native tertiary structure on the ribosome. By generating translation-arrested ribosomes in which the newly synthesized polypepticle chain is selectively C-13/N-15-labeled, we observe, using ultrafast NMR techniques, a large number of resonances of a ribosome-bound nascent chain complex corresponding to a pair of C-terminally truncated immunoglobulin (1g) domains. Analysis of these spectra reveals that the nascent chain adopts a structure in which a native-like N-tdrminal Ig domain is tethered to the ribosome by a largely unfolded and highly flexible C-terminal domain. Selective broadening of resonances for a group of residues that are colocalized in the structure demonstrates that there are specific but transient interactions between the ribosome and the N-terminal region of the folded Ig domain. These findings represent a step toward a detailed structural understanding of the cellular processes of cotranslational folding.
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页码:16516 / 16521
页数:6
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