Tang, Chao; Wang, Yadi; Cheng, Jie; Chang, Chao; Hu, Jun; Lu, Junhong

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

2022, 275, 1386-1425

Tang, Chao; Wang, Yadi; Cheng, Jie; Chang, Chao; Hu, Jun; Lu, Junhong

The development of meaningful descriptions of multidomain proteins exhibiting complex inter-domain dynamics modes is a key challenge for understanding their roles in molecular recognition and signalling processes. Here we developed a generally applicable approach for probing the low frequency collective hydration dynamics of multidomain proteins that uses terahertz spectroscopy of a protein molecule confined in a phospholipid reverse micelles environment (named Droplet THz). With the combination of normal mode analysis, we demonstrated the binding of calcium ions modulates the local inter-domain motion of the human coagulant factor VIII protein in a concentration-dependent manner. These findings highlight the Droplet THz as a valuable tool for dissecting the ultrafast dynamics of domain motion in the multidomain proteins and suggest a modulating mechanism of calcium ions on the structural flexibility and function of human coagulant proteins. (C) 2022 Elsevier B.V. All rights reserved.