TY - JOUR
T1 - The ribosome modulates folding inside the ribosomal exit tunnel
AU - Wruck, Florian
AU - Tian, Pengfei
AU - Kudva, Renuka
AU - Best, Robert B.
AU - von Heijne, Gunnar
AU - Tans, Sander J.
AU - Katranidis, Alexandros
PY - 2021
Y1 - 2021
N2 - Proteins commonly fold co-translationally at the ribosome, while the nascent chain emerges from the ribosomal exit tunnel. Protein domains that are sufficiently small can even fold while still located inside the tunnel. However, the effect of the tunnel on the folding dynamics of these domains is not well understood. Here, we combine optical tweezers with single-molecule FRET and molecular dynamics simulations to investigate folding of the small zinc-finger domain ADR1a inside and at the vestibule of the ribosomal tunnel. The tunnel is found to accelerate folding and stabilize the folded state, reminiscent of the effects of chaperonins. However, a simple mechanism involving stabilization by confinement does not explain the results. Instead, it appears that electrostatic interactions between the protein and ribosome contribute to the observed folding acceleration and stabilization of ADR1a.
AB - Proteins commonly fold co-translationally at the ribosome, while the nascent chain emerges from the ribosomal exit tunnel. Protein domains that are sufficiently small can even fold while still located inside the tunnel. However, the effect of the tunnel on the folding dynamics of these domains is not well understood. Here, we combine optical tweezers with single-molecule FRET and molecular dynamics simulations to investigate folding of the small zinc-finger domain ADR1a inside and at the vestibule of the ribosomal tunnel. The tunnel is found to accelerate folding and stabilize the folded state, reminiscent of the effects of chaperonins. However, a simple mechanism involving stabilization by confinement does not explain the results. Instead, it appears that electrostatic interactions between the protein and ribosome contribute to the observed folding acceleration and stabilization of ADR1a.
UR - http://www.scopus.com/inward/record.url?scp=85105395943&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-02055-8
DO - 10.1038/s42003-021-02055-8
M3 - Article
C2 - 33953328
AN - SCOPUS:85105395943
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 523
ER -