10.4225/03/57428DF17B655
SP Bottomley
SP
Bottomley
Ashley Buckle
Ashley
Buckle
RE Butcher
RE
Butcher
LD Cabrita
LD
Cabrita
KF Fulton
KF
Fulton
JA Irving
JA
Irving
AM Lesk
AM
Lesk
SL Reeve
SL
Reeve
Jamie Rossjohn
Jamie
Rossjohn
I Smith
I
Smith
James Whisstock
James
Whisstock
The high resolution crystal structure of a native thermostable serpin reveals the complex mechanism underpinning the stressed to relaxed transition.
Monash University
2016
serpine
Peptide Hydrolases
ImagingLocus
Molecular Biology
Biochemistry
2016-12-11 22:57:39
Dataset
https://bridges.monash.edu/articles/dataset/The_high_resolution_crystal_structure_of_a_native_thermostable_serpin_reveals_the_complex_mechanism_underpinning_the_stressed_to_relaxed_transition_/3123022
Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment. We have determined the 1.8 A x-ray crystal structure of thermopin in the native, inhibitory conformation. A structural comparison with the previously determined 1.5 A structure of cleaved thermopin provides detailed insight into the complex mechanism of conformational change in serpins. Flexibility in the shutter region and electrostatic interactions at the top of the A beta-sheet (the breach) involving the C-terminal tail, a unique structural feature of thermopin, are postulated to be important for controlling inhibitory activity and triggering conformational change, respectively, in the native state. Here we have discussed the structural basis of how this serpin reconciles the thermodynamic instability necessary for function with the stability required to withstand elevated temperatures.<br>