pH-Dependent Compaction of the Intrinsically Disordered Poly-E Motif in Titin.

Area of Science:

• Biochemistry
• Structural Biology
• Protein Chemistry

Background:

• Intrinsically disordered proteins (IDPs) exhibit conformational sensitivity to pH due to charged residues.
• The influence of non-ionizable residues on this pH sensitivity is not well understood.

Purpose of the Study:

• To investigate the role of non-ionizable residues in the pH sensitivity of intrinsically disordered proteins.
• To explore the impact of side-chain chemistry on the conformational flexibility of titin's PEVK region poly-E motifs.

Main Methods:

• Utilized 15-amino acid peptides from a titin poly-E motif sequence.
• Investigated the effects of introducing aromatic side chains and altering proline content on peptide conformation.
• Assessed conformational changes in response to pH variations.

Main Results:

• Aromatic side chains induced a more collapsed structure, even at neutral pH.
• Removal of proline residues increased the degree of pH sensitivity.
• Both aromaticity and proline content were identified as key modulators of pH sensitivity.

Conclusions:

• Non-ionizable residues play a crucial role in the pH-dependent conformational flexibility of IDPs.
• Understanding the contribution of all residue types is essential for predicting IDP function under varying pH conditions.