Two immunoglobulin tandem proteins with a linking β-strand reveal unexpected differences in cooperativity and folding pathways
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Two immunoglobulin tandem proteins with a linking β-strand reveal unexpected differences in cooperativity and folding pathways. / Steward, Annette; Chen, Qing; Chapman, Robert I.; Borgia, Madeleine B.; Rogers, Joseph M.; Wojtala, Alexsandra; Wilmanns, Matthias; Clarke, Jane.
In: Journal of Molecular Biology, Vol. 416, No. 1, 10.02.2012, p. 137-147.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Two immunoglobulin tandem proteins with a linking β-strand reveal unexpected differences in cooperativity and folding pathways
AU - Steward, Annette
AU - Chen, Qing
AU - Chapman, Robert I.
AU - Borgia, Madeleine B.
AU - Rogers, Joseph M.
AU - Wojtala, Alexsandra
AU - Wilmanns, Matthias
AU - Clarke, Jane
PY - 2012/2/10
Y1 - 2012/2/10
N2 - The study of the folding of single domains, in the context of their multidomain environment, is important because more than 70% of eukaryotic proteins are composed of multiple domains. The structures of the tandem immunoglobulin (Ig) domain pairs A164-A165 and A168-A169, from the A-band of the giant muscle protein titin, reveal that they form tightly associated domain arrangements, connected by a continuous β-strand. We investigate the thermodynamic and kinetic properties of these tandem domain pairs. While A164-A165 apparently behaves as a single cooperative unit at equilibrium, unfolding without the accumulation of a large population of intermediates, domains in A168-A169 behave independently. Although A169 appears to be stabilized in the tandem protein, we show that this is due to nonspecific stabilization by extension. We elucidate the folding and unfolding pathways of both tandem pairs and show that cooperativity in A164-A165 is a manifestation of the relative refolding and unfolding rate constants of each individual domain. We infer that the differences between the two tandem pairs result from a different pattern of interactions at the domain/domain interface.
AB - The study of the folding of single domains, in the context of their multidomain environment, is important because more than 70% of eukaryotic proteins are composed of multiple domains. The structures of the tandem immunoglobulin (Ig) domain pairs A164-A165 and A168-A169, from the A-band of the giant muscle protein titin, reveal that they form tightly associated domain arrangements, connected by a continuous β-strand. We investigate the thermodynamic and kinetic properties of these tandem domain pairs. While A164-A165 apparently behaves as a single cooperative unit at equilibrium, unfolding without the accumulation of a large population of intermediates, domains in A168-A169 behave independently. Although A169 appears to be stabilized in the tandem protein, we show that this is due to nonspecific stabilization by extension. We elucidate the folding and unfolding pathways of both tandem pairs and show that cooperativity in A164-A165 is a manifestation of the relative refolding and unfolding rate constants of each individual domain. We infer that the differences between the two tandem pairs result from a different pattern of interactions at the domain/domain interface.
KW - Beta sheet
KW - multidomain
KW - protein folding
KW - tandem repeat
KW - titin A-band
UR - http://www.scopus.com/inward/record.url?scp=84856433534&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2011.12.012
DO - 10.1016/j.jmb.2011.12.012
M3 - Journal article
C2 - 22197372
AN - SCOPUS:84856433534
VL - 416
SP - 137
EP - 147
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 1
ER -
ID: 244651557