Macromolecular mimicry in protein biosynthesis

TY - JOUR

T1 - Macromolecular mimicry in protein biosynthesis

AU - Nyborg, J

AU - Nissen, P

AU - Kjeldgaard, M

AU - Thirup, S

AU - Polekhina, G

AU - Clark, B F

AU - Reshetnikova, L

PY - 1997

Y1 - 1997

N2 - Elongation factor Tu (EF-Tu) is a G-protein which, in its active GTP conformation, protects and carries aminoacylated tRNAs (aa-tRNAs) to the ribosome during protein biosynthesis. EF-Tu consists of three structural domains of which the N-terminal domain consists of two special regions (switch I and switch II) which are structurally dependent on the type of the bound nucleotide. Structural studies of the complete functional cycle of EF-Tu reveal that it undergoes rather spectacular conformational changes when activated from the EF-Tu.GDP form to the EF-Tu.GTP form. In its active form, EF-Tu.GTP without much further structural change interacts with aa-tRNAs in the so-called ternary complex. The conformational changes of EF-Tu involve rearrangements of the secondary structures of both the switch I and switch II regions. As the switch II region forms part of the interface between domains 1 and 3, its structural rearrangement results in a very large change of the position of domain 1 relative to domains 2 and 3. The overall shape of the ternary complex is surprisingly similar to the overall shape of elongation factor G (EF-G). Thus, three domains of the protein EF-G seem to mimic the tRNA part of the ternary complex. This macromolecular mimicry has profound implications for the function of the elongation factors on the ribosome.

AB - Elongation factor Tu (EF-Tu) is a G-protein which, in its active GTP conformation, protects and carries aminoacylated tRNAs (aa-tRNAs) to the ribosome during protein biosynthesis. EF-Tu consists of three structural domains of which the N-terminal domain consists of two special regions (switch I and switch II) which are structurally dependent on the type of the bound nucleotide. Structural studies of the complete functional cycle of EF-Tu reveal that it undergoes rather spectacular conformational changes when activated from the EF-Tu.GDP form to the EF-Tu.GTP form. In its active form, EF-Tu.GTP without much further structural change interacts with aa-tRNAs in the so-called ternary complex. The conformational changes of EF-Tu involve rearrangements of the secondary structures of both the switch I and switch II regions. As the switch II region forms part of the interface between domains 1 and 3, its structural rearrangement results in a very large change of the position of domain 1 relative to domains 2 and 3. The overall shape of the ternary complex is surprisingly similar to the overall shape of elongation factor G (EF-G). Thus, three domains of the protein EF-G seem to mimic the tRNA part of the ternary complex. This macromolecular mimicry has profound implications for the function of the elongation factors on the ribosome.

KW - Amino Acid Sequence

KW - Guanosine Diphosphate

KW - Guanosine Triphosphate

KW - Macromolecular Substances

KW - Models, Molecular

KW - Molecular Mimicry

KW - Molecular Sequence Data

KW - Peptide Chain Elongation, Translational

KW - Peptide Elongation Factor Tu

KW - Protein Biosynthesis

KW - Protein Folding

KW - Protein Structure, Secondary

KW - Sequence Homology, Amino Acid

M3 - Journal article

C2 - 9218959

SN - 0969-2126

VL - 2

SP - S7-11

JO - Structure

JF - Structure

IS - 3

ER -