TY - JOUR
T1 - Action of a minimal contractile bactericidal nanomachine
AU - Ge, Peng
AU - Scholl, Dean
AU - Prokhorov, Nikolai S.
AU - Avaylon, Jaycob
AU - Shneider, Mikhail M.
AU - Browning, Christopher
AU - Buth, Sergey A.
AU - Plattner, Michel
AU - Chakraborty, Urmi
AU - Ding, Ke
AU - Leiman, Petr G.
AU - Miller, Jeff F.
AU - Zhou, Z. Hong
N1 - Funding Information:
Acknowledgements We thank X. Yu for advice in sample purification; UCLA students K. Wang, L. Nguyen, R. Chi, N. Poweleit and P. Graybeal and Beverly Hills High School students J. Gunn and L. Wang for picking particles; UCLA student E. Brown for video editing support; and D. Martin of AvidBiotics for discussion and support throughout this project. This research was supported in part by the NIH (R01GM071940 to Z.H.Z. and R21AI085318 to D.S.), the Swiss National Science Foundation (31003A_146284 to P.G.L.), and the Schaffer Family Foundation and Kavli Endowment (to J.F.M.). P.G. was supported in part by the American Heart Association Western States Affiliates Postdoc Fellowship (13POST17340020). We acknowledge the use of resources at the Electron Imaging Center for Nanomachines (EICN; supported by UCLA and by instrumentation grants from the NIH (1S10OD018111 and 1U24GM116792) and the NSF (DBI-1338135 and DMR-1548924)) and computation resource at the Extreme Science and Engineering Discovery Environment (XSEDE grant MCB140140 to Z.H.Z.). Recharge fees for access to the EICN facility for imaging the pyocin samples were partially defrayed by an award to Z.H.Z. from the UCLA CTSI core voucher program.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/4/30
Y1 - 2020/4/30
N2 - R-type bacteriocins are minimal contractile nanomachines that hold promise as precision antibiotics1–4. Each bactericidal complex uses a collar to bridge a hollow tube with a contractile sheath loaded in a metastable state by a baseplate scaffold1,2. Fine-tuning of such nucleic acid-free protein machines for precision medicine calls for an atomic description of the entire complex and contraction mechanism, which is not available from baseplate structures of the (DNA-containing) T4 bacteriophage5. Here we report the atomic model of the complete R2 pyocin in its pre-contraction and post-contraction states, each containing 384 subunits of 11 unique atomic models of 10 gene products. Comparison of these structures suggests the following sequence of events during pyocin contraction: tail fibres trigger lateral dissociation of baseplate triplexes; the dissociation then initiates a cascade of events leading to sheath contraction; and this contraction converts chemical energy into mechanical force to drive the iron-tipped tube across the bacterial cell surface, killing the bacterium.
AB - R-type bacteriocins are minimal contractile nanomachines that hold promise as precision antibiotics1–4. Each bactericidal complex uses a collar to bridge a hollow tube with a contractile sheath loaded in a metastable state by a baseplate scaffold1,2. Fine-tuning of such nucleic acid-free protein machines for precision medicine calls for an atomic description of the entire complex and contraction mechanism, which is not available from baseplate structures of the (DNA-containing) T4 bacteriophage5. Here we report the atomic model of the complete R2 pyocin in its pre-contraction and post-contraction states, each containing 384 subunits of 11 unique atomic models of 10 gene products. Comparison of these structures suggests the following sequence of events during pyocin contraction: tail fibres trigger lateral dissociation of baseplate triplexes; the dissociation then initiates a cascade of events leading to sheath contraction; and this contraction converts chemical energy into mechanical force to drive the iron-tipped tube across the bacterial cell surface, killing the bacterium.
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U2 - 10.1038/s41586-020-2186-z
DO - 10.1038/s41586-020-2186-z
M3 - Article
C2 - 32350467
AN - SCOPUS:85083453757
SN - 0028-0836
VL - 580
SP - 658
EP - 662
JO - Nature
JF - Nature
IS - 7805
ER -