Evolution of Transthyretin

TL;DR

This paper explores how the evolution of transthyretin's amino acid sequences influences its dynamics, highlighting the role of water interactions and mutations in its stability and disease-related regions.

Contribution

It links protein sequence evolution to dynamic behavior and water interactions, revealing mutation patterns related to amyloid polyneuropathy.

Findings

Water wave profiles connect domain pivots and hydrophilic regions.

The central hinge region shows higher mutation density.

Evolutionary changes enhance TTR flexibility and stability.

Abstract

Evolution of the amino acid sequences of transthyretin (TTR) can provide additional information about its dynamics that both complements and extends the already extensive static structural data. Protein dynamics is largely driven by interactions between the protein itself and the thin water film that covers it. Here those interactions are connected to profiles of water waves connecting domain pivots (hydrophobic extrema), as well as a broad hydrophilic central hinge region that has evolved to provide human TTR with greater flexibility and stability. This central region has a density of single mutations related to amyloid polyneuropathy that is three times higher than other regions.