Yu-Chen Chang

Order–disorder transitions allow many proteins to shift between compact and flexible/unfolded states, thereby acting as structural switches that regulate catalysis, signaling, recognition, and allostery. We applied time-resolved serial oscillation crystallography to establish the structural kinetics of the light-triggered order–disorder transition of an animal-like cryptochrome as a six-second-long molecular movie with near-atomic all-residue spatial resolution and millisecond temporal resolution. Our 29 structural snapshots mapped the propagation of disorder across the tertiary structure motifs of a cryptochrome’s C-terminal region, triggered by a single broken D321–R492 salt bridge. The order–disorder transition followed a nucleation-propagation mechanism reminiscent of helix–coil dynamics and proceeded over up to five seconds, with regions distal to the D321–R492 trigger initially undergoing slow zero-order disordering before switching to first-order unfolding kinetics. Our per-residue density analysis provides a detailed structural-kinetic basis for understanding how order–disorder transitions emerge through directional propagation across protein tertiary structures, as occurring in signaling and many other biological systems.

Mechanically responsive molecular crystals offer a powerful platform for transducing molecular motion into macroscopic mechanical work, yet molecular‐level understanding of how crystal structures govern molecular motion and, consequently, mechanical behavior remains limited. A notable example is the anthracene‐pentiptycene‐semifluorinated alkyl crystal 1‐F4 , recently reported to exhibit large elastic bending (ε ≈ 12%) and >15% photoinduced crystal expansion without fracture. Here, we investigate a homologous crystal series ( 1‐F n , n = 2, 3, 4, and 6) and reveal a mechanically coupled supramolecular scissoring motion that governs their diverse mechanical responses. The balance between scissor stretchability and compressibility, tuned by semifluorinated alkyl substituents, dictates the deformation mode, elasticity, and crystal integrity. An optimally balanced scissor state in 1‐F4 enables exceptional elastic and photomechanical deformation while preserving crystal integrity, whereas fully‐extended ( 1‐F2 ), over‐contracted ( 1‐F6 ), or mechanically unbalanced ( 1‐F3 ) scissor states lead to brittle failure or explosive photosalient behavior. These results establish a direct structure−motion−property relationship within this homologous series, demonstrating that key mechanical properties, including deformation mode and elastic limit, are encoded in the initial scissor geometry within the crystal packing arrangement.

Mechanically responsive molecular crystals offer a powerful platform for transducing molecular motion into macroscopic mechanical work, yet molecular‐level understanding of how crystal structures govern molecular motion and, consequently, mechanical behavior remains limited. A notable example is the anthracene‐pentiptycene‐semifluorinated alkyl crystal 1‐F4 , recently reported to exhibit large elastic bending (ε ≈ 12%) and >15% photoinduced crystal expansion without fracture. Here, we investigate a homologous crystal series ( 1‐F n , n = 2, 3, 4, and 6) and reveal a mechanically coupled supramolecular scissoring motion that governs their diverse mechanical responses. The balance between scissor stretchability and compressibility, tuned by semifluorinated alkyl substituents, dictates the deformation mode, elasticity, and crystal integrity. An optimally balanced scissor state in 1‐F4 enables exceptional elastic and photomechanical deformation while preserving crystal integrity, whereas fully‐extended ( 1‐F2 ), over‐contracted ( 1‐F6 ), or mechanically unbalanced ( 1‐F3 ) scissor states lead to brittle failure or explosive photosalient behavior. These results establish a direct structure−motion−property relationship within this homologous series, demonstrating that key mechanical properties, including deformation mode and elastic limit, are encoded in the initial scissor geometry within the crystal packing arrangement.

Photolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci. We used these results to create a movie that depicts the repair of CPD lesions in the picosecond-to-nanosecond range, followed by the recovery of the enzymatic moieties involved in catalysis, completing the formation of the fully reduced enzyme-product complex at 500 nanoseconds. Finally, back-flip intermediates of the thymine bases to reanneal the DNA were captured at 25 to 200 microseconds. Our data cover the complete molecular mechanism of a photolyase and, importantly, its chemistry and enzymatic catalysis at work across a wide timescale and at atomic resolution.