Nanomechanics of intrinsically disordered proteins: interplay of force, form and function

K. Wang
Academia Sinica, TW

Keywords: nanomechanics, protein elasticity, intrinsically disordered proteins, atomic force microscopy


Proteins and protein domains that lack unique folds are essential participants in a variety of biological processes. How these intrinsically disordered proteins in catalysis, in the assembly of complexes and in cellular signaling are emerging themes in structural biology. As part of long term interest of investigating the structural biology and function of titin and nebulin, two of the largest proteins in human proteome that we discovered some years ago, we have established a technical platform to understand the interplay between the force, form and function of the intrinsically disordered regions of these elastic proteins and made some major conceptual advances. The key concept is that the nanomechanical properties of IDP are critically important in how they function in the signaling pathways and force signals are transduced to biochemical and cellular processes. The technical platform includes protein engineering of polyproteins with built-in force handles, conformational studies in solution and on surface by NMR, force microscopy and single molecule imaging by AFM, simulated molecular dynamics, adaptive data analysis technique and other computational techniques. The structural transitions of force events during protein stretching, especially those of IDP, provide unique insights in the dynamics signaling pathways under mechanical stress.