Open Access
ACS Chemical Biology, volume 9, issue 11, pages 2621-2631
Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome
Washington Arren Z
1
,
Benicewicz Derek B
1
,
Canzoneri Joshua C.
1
,
Fagan Crystal E
2
,
Mwakwari Sandra C.
1
,
Maehigashi Tatsuya
2
,
Dunham C. Michael
2
,
Oyelere Adegboyega K
1
2
Department
of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, United States
|
Publication type: Journal Article
Publication date: 2014-09-22
Journal:
ACS Chemical Biology
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 4
ISSN: 15548929, 15548937
PubMed ID:
25198768
Biochemistry
General Medicine
Molecular Medicine
Abstract
Despite decades of research on the bacterial ribosome, the ribosomal exit tunnel is still poorly understood. Although it has been suggested that the exit tunnel is simply a convenient route of egress for the nascent chain, specific protein sequences serve to slow the rate of translation, suggesting some degree of interaction between the nascent peptide chain and the exit tunnel. To understand how the ribosome interacts with nascent peptide sequences, we synthesized and characterized a novel class of probe molecules. These peptide–macrolide (or “peptolide”) conjugates were designed to present unique peptide sequences to the exit tunnel. Biochemical and X-ray structural analyses of the interactions between these probes and the ribosome reveal interesting insights about the exit tunnel. Using translation inhibition and RNA structure probing assays, we find the exit tunnel has a relaxed preference for the directionality (N → C or C → N orientation) of the nascent peptides. Moreover, the X-ray crystal structure of one peptolide derived from a positively charged, reverse Nuclear Localization Sequence peptide, bound to the 70S bacterial ribosome, reveals that the macrolide ring of the peptolide binds in the same position as other macrolides. However, the peptide tail folds over the macrolide ring, oriented toward the peptidyl transferase center and interacting in a novel manner with 23S rRNA residue C2442 and His69 of ribosomal protein L4. These data suggest that these peptolides are viable probes for interrogating nascent peptide–exit tunnel interaction.
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Citations by publishers
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Washington A. Z. et al. Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome // ACS Chemical Biology. 2014. Vol. 9. No. 11. pp. 2621-2631.
GOST all authors (up to 50)
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Washington A. Z., Benicewicz D. B., Canzoneri J. C., Fagan C. E., Mwakwari S. C., Maehigashi T., Dunham C. M., Oyelere A. K. Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome // ACS Chemical Biology. 2014. Vol. 9. No. 11. pp. 2621-2631.
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TY - JOUR
DO - 10.1021/cb5003224
UR - https://doi.org/10.1021%2Fcb5003224
TI - Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome
T2 - ACS Chemical Biology
AU - Washington, Arren Z
AU - Benicewicz, Derek B
AU - Canzoneri, Joshua C.
AU - Fagan, Crystal E
AU - Mwakwari, Sandra C.
AU - Oyelere, Adegboyega K
AU - Maehigashi, Tatsuya
AU - Dunham, C. Michael
PY - 2014
DA - 2014/09/22 00:00:00
PB - American Chemical Society (ACS)
SP - 2621-2631
IS - 11
VL - 9
PMID - 25198768
SN - 1554-8929
SN - 1554-8937
ER -
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@article{2014_Washington,
author = {Arren Z Washington and Derek B Benicewicz and Joshua C. Canzoneri and Crystal E Fagan and Sandra C. Mwakwari and Adegboyega K Oyelere and Tatsuya Maehigashi and C. Michael Dunham},
title = {Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome},
journal = {ACS Chemical Biology},
year = {2014},
volume = {9},
publisher = {American Chemical Society (ACS)},
month = {sep},
url = {https://doi.org/10.1021%2Fcb5003224},
number = {11},
pages = {2621--2631},
doi = {10.1021/cb5003224}
}
Cite this
MLA
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Washington, Arren Z., et al. “Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome.” ACS Chemical Biology, vol. 9, no. 11, Sep. 2014, pp. 2621-2631. https://doi.org/10.1021%2Fcb5003224.