TY - JOUR
T1 - DMSO-induced denaturation of hen egg white lysozyme
AU - Voets, Ilja K.
AU - Cruz, Willemberg A.
AU - Moitzi, Christian
AU - Lindner, Peter
AU - Arêas, Elizabeth P.G.
AU - Schurtenberger, Peter
PY - 2010/9/16
Y1 - 2010/9/16
N2 - We report on the size, shape, structure, and interactions of lysozyme in the ternary system lysozyme/DMSO/water at low protein concentrations. Three structural regimes have been identified, which we term the "folded" (0 < DMSO < 0.7), "unfolded" (0.7 ≤ DMSO < 0.9), and "partially collapsed" (0.9 ≤ DMSO < 1.0) regime. Lysozyme resides in a folded conformation with an average radius of gyration of 1.3 ± 0.1 nm for DMSO < 0.7 and unfolds (average Rg of 2.4 ± 0.1 nm) above DMSO > 0.7. This drastic change in the protein's size coincides with a loss of the characteristic tertiary structure. It is preceded by a compaction of the local environment of the tryptophan residues and accompanied by a large increase in the protein's overall flexibility. In terms of secondary structure, there is a gradual loss of α-helix and concomitant increase of β-sheet structural elements toward DMSO = 0.7, while an increase in DMSO at even higher DMSO volume fractions reduces the presence of both α-helix and β-sheet secondary structural elements. Protein-protein interactions remain overall repulsive for all values of DMSO. An attempt is made to relate these structural changes to the three most important physical mechanisms that underlie them: the DMSO/water microstructure is strongly dependent on the DMSO volume fraction, DMSO acts as a strong H-bond acceptor, and DMSO is a bad solvent for the protein backbone and a number of relatively polar side groups, but a good solvent for relatively apolar side groups, such as tryptophan.
AB - We report on the size, shape, structure, and interactions of lysozyme in the ternary system lysozyme/DMSO/water at low protein concentrations. Three structural regimes have been identified, which we term the "folded" (0 < DMSO < 0.7), "unfolded" (0.7 ≤ DMSO < 0.9), and "partially collapsed" (0.9 ≤ DMSO < 1.0) regime. Lysozyme resides in a folded conformation with an average radius of gyration of 1.3 ± 0.1 nm for DMSO < 0.7 and unfolds (average Rg of 2.4 ± 0.1 nm) above DMSO > 0.7. This drastic change in the protein's size coincides with a loss of the characteristic tertiary structure. It is preceded by a compaction of the local environment of the tryptophan residues and accompanied by a large increase in the protein's overall flexibility. In terms of secondary structure, there is a gradual loss of α-helix and concomitant increase of β-sheet structural elements toward DMSO = 0.7, while an increase in DMSO at even higher DMSO volume fractions reduces the presence of both α-helix and β-sheet secondary structural elements. Protein-protein interactions remain overall repulsive for all values of DMSO. An attempt is made to relate these structural changes to the three most important physical mechanisms that underlie them: the DMSO/water microstructure is strongly dependent on the DMSO volume fraction, DMSO acts as a strong H-bond acceptor, and DMSO is a bad solvent for the protein backbone and a number of relatively polar side groups, but a good solvent for relatively apolar side groups, such as tryptophan.
UR - http://www.scopus.com/inward/record.url?scp=77956544186&partnerID=8YFLogxK
U2 - 10.1021/jp103515b
DO - 10.1021/jp103515b
M3 - Article
AN - SCOPUS:77956544186
SN - 1520-6106
VL - 114
SP - 11875
EP - 11883
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 36
ER -