Abstract
Nascent polypeptide chains fold cotranslationally, but the atomic‐level details of this process remain unknown. Here, we report crystallographic, de novo modeling, and spectroscopic studies of intermediate‐length variants of the λ repressor N‐terminal domain. Although the ranges of helical regions of the half‐length variant were almost identical to those of the full‐length protein, the relative orientations of these helices in the intermediate‐length variants differed. Our results suggest that cotranslational folding of the λ repressor initially forms a helical structure with a transient conformation, as in the case of a molten globule state. This conformation subsequently matures during the course of protein synthesis.DatabaseStructural data are available in the PDB under the accession numbers http://www.rcsb.org/pdb/search/structidSearch.do?structureId=5ZCA and http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3WOA.
Highlights
Proteins are synthesized on the ribosomes and fold into thermodynamically stable structures
The helical region of k1–20, which contains a portion of helix 1 of the full-length k repressor, was almost the same as that of the full-length protein. k1–20 and the full-length proteins (PDBID: 1LMB) could be superimposed on each other with a root-mean-square deviation (RMSD) of 0.77 A. k1–45 formed a helical conformation, whose regions are almost identical to those of the fulllength protein
Our crystallographic results showed that the k repressor of N-terminal fragments could fold into helical structures with lengths of 20 and 45 residues
Summary
Proteins are synthesized on the ribosomes and fold into thermodynamically stable structures. Various intermediate states of nascent proteins can exist for a long period because the timescale of the cotranslational folding (on the order of seconds to minutes) is much longer than that of the full-length protein folding (on the order of microseconds) [6]. The characterizations of the intermediate states of nascent proteins are important to understand the process of the cotranslational folding. The intermediate-length fragments formed helical structures even though the full-length protein has no helical regions. This suggests a structural change from a structure in which short-range interactions are decisive to one in which long-range interactions of a particular peptide length are decisive. The nascent proteins eventually reach the native structures by adopting stable transient conformations
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