TY - JOUR
T1 - pH-Dependent Compaction of the Intrinsically Disordered Poly-E Motif in Titin
AU - Manukian, Sophia
AU - Lindberg, Gerrick E.
AU - Punch, Emily
AU - Mudiyanselage, Sudarshi Premawardhana Dassanayake
AU - Gage, Matthew J
N1 - Funding Information:
This research was funded by the National Institutes of Health, grant number R15GM132840-01.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - The conformational sensitivity of intrinsically disordered proteins to shifts in pH due to their high degree of charged residues has been recognized for well over a decade. However, the role of the non-ionizable residues in this pH sensitivity remains poorly understood. Our lab has been investigating the pH sensitivity of the poly-E motifs of the PEVK region of the muscle protein titin, which provides an ideal model system to explore this question. Using a series of 15-amino acid peptides derived from one of the poly-E motif sequences, we have investigated the role of side-chain chemistry in the conformational flexibility of this region. Our results demonstrate that aromatic side chains and proline content are the two variables that most influence pH sensitivity. The introduction of aromatic side chains resulted in a more collapsed structure, even at pH 7, while the removal of prolines resulted in a higher degree of pH sensitivity. These results highlight the importance of considering the impact of non-ionizable residues on IDP function, especially when considering the impact of pH on conformational flexibility.
AB - The conformational sensitivity of intrinsically disordered proteins to shifts in pH due to their high degree of charged residues has been recognized for well over a decade. However, the role of the non-ionizable residues in this pH sensitivity remains poorly understood. Our lab has been investigating the pH sensitivity of the poly-E motifs of the PEVK region of the muscle protein titin, which provides an ideal model system to explore this question. Using a series of 15-amino acid peptides derived from one of the poly-E motif sequences, we have investigated the role of side-chain chemistry in the conformational flexibility of this region. Our results demonstrate that aromatic side chains and proline content are the two variables that most influence pH sensitivity. The introduction of aromatic side chains resulted in a more collapsed structure, even at pH 7, while the removal of prolines resulted in a higher degree of pH sensitivity. These results highlight the importance of considering the impact of non-ionizable residues on IDP function, especially when considering the impact of pH on conformational flexibility.
KW - PEVK
KW - circular dichroism
KW - conformational change
KW - intrinsically disordered proteins
KW - titin
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U2 - 10.3390/biology11091302
DO - 10.3390/biology11091302
M3 - Article
AN - SCOPUS:85138672802
SN - 2079-7737
VL - 11
JO - Biology
JF - Biology
IS - 9
M1 - 1302
ER -