Transient Non-local Interactions Dominate the Dynamics of Measles Virus NTAIL
Lillian Otteson1,2, Gabor Nagy3, John Kunkel1,2
1Center for Biological Physics, Arizona State University, Tempe, AZ, USA.
Biorxiv : the Preprint Server for Biology
|August 2, 2024
Summary
Measles virus nucleoprotein
Area of Science:
- Virology
- Structural Biology
- Biophysics
Background:
- Measles virus RNA genome is protected by nucleoprotein in a helical nucleocapsid.
- The nucleoprotein's disordered tail (NTAIL) binds the polymerase complex for transcription and replication.
- NTAIL binding involves a short molecular recognition element (MoRE) that folds upon interaction.
Purpose of the Study:
- Investigate the influence of distant NTAIL regions on polymerase binding affinity.
- Elucidate the dynamics and interactions within the disordered NTAIL domain.
- Understand how intramolecular interactions regulate NTAIL function in measles virus replication.
Main Methods:
- Integrated approach combining photo-induced electron transfer (PET) experiments.
- Tryptophan-cysteine pair analysis under varying salt and pH conditions.
- Molecular dynamics simulations and analytical modeling.
- Co-evolutionary analysis of protein sequences.
Main Results:
- Identified transient, non-local interactions between distant disordered regions in NTAIL.
- These interactions significantly influence NTAIL dynamics and the conformational state of the MoRE.
- Co-evolutionary analysis supports the functional importance of these intramolecular interactions.
Conclusions:
- Non-local interactions within NTAIL are crucial for regulating its dynamics and binding properties.
- These interactions likely modulate polymerase recruitment and viral transcription/replication.
- Findings offer insights into the mechanisms of intrinsically disordered proteins (IDPs) in viral processes and beyond.
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