Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Wednesday Speaker Abstracts

THE ROLE OF CONFORMATIONAL ENTROPY IN INTEGRAL MEMBRANE PROTEIN BIOPHYSICS Kelly Risch 1 ; Taylor Razor Cole 1 ; Joshua Wand 1 ; 1 Texas A&M University, Biochemistry and Biophysics, College Station, TX, USA Understanding the motions of amino acid side chains is crucial for a complete picture of the thermodynamics governing protein stability, structure, and function. Here we focus on the conformational entropy manifested in sub-nanosecond motion. Using an NMR relaxation-based approach, we have shown that changes in conformational entropy in soluble proteins can be a pivotal contribution to the thermodynamics of protein structure-function relationships, either favorably or unfavorably. 1,2 We have overcome several technical barriers that have historically hindered similar investigation of integral membrane proteins (IMPs). In the first examples, we found that photo sensory rhodopsin II and outer membrane protein W are more dynamic that any soluble protein studied in this way. 3 This degree of side chain motion corresponds to an extraordinary level of conformational entropy and helps explain the stability of the folded state in the absence of the hydrophobic effect. 4 The role of this “excess” entropy in the thermodynamics of molecular recognition by IMPs remains a mystery. We are continuing to investigate the nature of internal motion and conformational entropy of IMPs and their sensitivity to the host membrane mimetic such as micelles, bicelles and nanodiscs. Results from similar studies of human VDAC-1 in nanodiscs also show the dynamic signature of the previous study. Supported by Texas A&M University, the NIH and the Mathers Foundation.Caro et al (2017) Proc. Nat. Acad. Sci. USA 114, 6563.Wand & Sharp (2018) Annu. Rev. Biophys. 47, 4. O’Brien et al (2020) Angewandte Chemi Intl. Ed. 59, 11108Corin & Bowie, J.U. (2022) EMBO Rep. 23, e53025


Made with FlippingBook flipbook maker