Sara Vaiana, PhD

Arizona State University

 

Dynamical heterogeneity in intrinsically disordered proteins: is disorder a new key to life?

 

Living systems display a great deal of order, from the macroscopic to the microscopic level. This is evident if you observe the structures inside a cell, or zoom-in to the building blocks and molecular machines within them. In fact, our entire understanding of proteins is based on the assumption that their 3D structure enables their biological function. However, this view has changed since the discovery of Intrinsically Disordered Proteins (IDPs), proteins that carry out complex biological functions, yet lack a stable 3D structure. IDPs play a key role in vital cell processes, including transcription and replication, signaling, and the formation of membrane-less organelles. As a consequence, they are implicated in a wide range of diseases, from cancer, to viral infection, to metabolic and neurological diseases. I will describe the exciting experimental and theoretical challenges we face in building a quantitative biophysical understanding of IDPs, and the progress made in the field by combining experiments, theory, and simulations. As an example, I will discuss combining photo-induced electron transfer (PET) experiments, with analytical polymer models, coarse-grained and all atom simulations, to study two very different systems: the Measles virus nucleoprotein NTAIL, responsible for viral transcription and replication; and electrostatic interactions in hormone IDPs of the calcitonin family, implicated in diabetes and migraine headaches.