Protein aggregation from inclusion bodies to amyloid and biomaterials

Abstract

Inclusion bodies and amyloid are two different outcomes of the same fundamental biological process: protein aggregation. They share two important features that suggest sequence-specific aggregation: oligomeric intermediates as precursors to the aggregated sate and sensitivity to site-specific point mutations. For a long time, the physical state of inclusion bodies was refractory to the use of protein structural characterization techniques that were developed for soluble proteins. Recent high-resolution studies reveal that the apparently amorphous state of these dense protein agglomerates consists of amyloid-type structures adopted by short segments that initiate aggregation. Under certain circumstances it is possible for the aggregation-prone segments to "recruit" a globular counterpart within the inclusion body, with the latter being able to fold into an active conformation. In this chapter we will discuss these recent structural insights in relation with the also recent, high-resolution structures for amyloid "spines" and their ability to accommodate globular or "swapped" domains in their periphery. Finally, unexpected natural roles for amyloid structures such as protection, adhesion, and storage materials gradually emerge. We will discuss how these properties in combination with biochemical and structural insights can inspire "biomimetic" approaches for the rational design of novel nanobiomaterials.