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Ribosomal signature

Ribosomal signature. Conserved & Characteristic positions on the ribosome. Assembly initiation site. Peptidyl transferase center. Adapted from Roberts et al. PNAS 2008. Q:. Evolutionary pressure?. Function in modern ribosome?. Signature function scenario I: Small Subunit Assembly.

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Ribosomal signature

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  1. Ribosomal signature Conserved & Characteristic positions on the ribosome Assembly initiation site Peptidyltransferase center Adapted from Roberts et al. PNAS 2008 Q: Evolutionary pressure? Function in modern ribosome?

  2. Signature function scenario I: Small Subunit Assembly • R-protein S4: primary binding and initiator protein • Five-way junction (5WJ): with abundant experimental data R-protein S4

  3. Pulse-chase experiments monitored by quantitative mass spectrometry Mulder et al. Science 2010 Hydroxyl radical footprinting Nomura Map Experiments Ramaswamy et al. Nature 2009 Held et al. J. Biol. Chem. 1974 Selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) Single-molecule FRET Ha et al. PNAS 1999 Mayerle et al. JMB 2011

  4. With Molecular Dynamics Simulation… 50 nanoseconds ~200 processors ~10 days Can we do BETTER?

  5. NOW, With Go-potential Simulation… ~6 processors ~10 hours A Hundred replicates over-night!

  6. Multiple pathways & intermediates Binding intermediate II Near-folded state Binding intermediate I

  7. Signature function scenario II: Peptidyltransferase center (PTC)

  8. Models Evolutionary perspective Symmetry Stability & Structural signatures Sequence signatures Model 1 Model 2

  9. Models Evolutionary perspective Symmetry Stability & Model 1: likely the initial form of PTC that is able to catalyze a peptide bond ANTON! -- without substrate 186 ns -- with both A- and P- site substrates: A-Phe 82 ns -- with both A- and P- site substrates: CpCpA-Phe 125 ns Model 2: additional loops to hold larger substrates, probably a later invention in evolution -- without substrate 210 ns -- with both A- and P- site substrates: CpCpA-Phe 185 ns

  10. Model stability Model 1: early PTC

  11. Model stability Model 2: more complete model

  12. More evidence? Angle between the two arms for both A- and P-cores A-core(blue): trying to be more compact P-core(green): flattening out Model 1: early PTC

  13. Hypothesis: Symmetric structure Asymmetric dynamics Asymmetric functions A-core for substrate positioning P-core for substrate movement

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