Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution

Area of Science:

• Biochemistry and Structural Biology
• Protein Dynamics and Molecular Recognition

Background:

• Protein dynamics are crucial for function, but studying atomic motions in solution (nanosecond-to-microsecond timescale) is challenging.
• Understanding these dynamics is key to deciphering protein interactions and functions.

Purpose of the Study:

• To present a refined structural ensemble of ubiquitin capturing solution dynamics up to microseconds.
• To investigate the role of protein dynamics in ubiquitin's molecular recognition and complex formation.

Main Methods:

• Refinement of a ubiquitin structural ensemble using residual dipolar couplings (RDCs).
• Analysis of the ensemble to cover structural heterogeneity observed in crystal structures.
• Correlation analysis between protein flexibility and complex formation contacts.

Main Results:

• The study presents a ubiquitin ensemble reflecting solution dynamics on nanosecond-to-microsecond timescales.
• Conformational selection, not induced fit, explains ubiquitin's molecular recognition.
• Protein flexibility correlates with ubiquitin complex contacts, driven by a dominant concerted motion.

Conclusions:

• Ubiquitin's molecular recognition relies on conformational selection, utilizing its inherent flexibility.
• A major dynamic mode in ubiquitin explains its recognition heterogeneity and reduces entropic costs in complex formation.
• This work provides insights into protein dynamics and molecular recognition mechanisms.