TY - JOUR
T1 - Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin
AU - Molugu, Sudheer K.
AU - Hildenbrand, Zacariah L.
AU - Morgan, David Gene
AU - Sherman, Michael B.
AU - He, Lilin
AU - Georgopoulos, Costa
AU - Sernova, Natalia V.
AU - Kurochkina, Lidia P.
AU - Mesyanzhinov, Vadim V.
AU - Miroshnikov, Konstantin A.
AU - Bernal, Ricardo A.
N1 - Funding Information:
This work was supported by NIH- NIGMS SC3GM113805 , NSF - MRI 0923437 and Welch Foundation grant AH–1649 to Ricardo A. Bernal and Russian Fund for Basic Research grant # 11-04-00935 to Lidia P. Kurochkina. We would like to thank Dr. Judy Ellzey and Dr. Peter Cooke, Director of the New Mexico State University EM facility for his help with negative stain transmission electron microscopy. The Bio-SANS of the Center for Structural Molecular Biology (FWP ERKP291) at Oak Ridge National Laboratory is supported by the Office of Biological and Environmental Research of the US Department of Energy. Research at the High Flux Isotope Reactor of Oak Ridge National Laboratory was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences , US Department of Energy.
Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.
PY - 2016/4/5
Y1 - 2016/4/5
N2 - Chaperonins are ubiquitous, ATP-dependent protein-folding molecular machines that are essential for all forms of life. Bacteriophage φEL encodes its own chaperonin to presumably fold exceedingly large viral proteins via profoundly different nucleotide-binding conformations. Our structural investigations indicate that ATP likely binds to both rings simultaneously and that a misfolded substrate acts as the trigger for ATP hydrolysis. More importantly, the φEL complex dissociates into two single rings resulting from an evolutionarily altered residue in the highly conserved ATP-binding pocket. Conformational changes also more than double the volume of the single-ring internal chamber such that larger viral proteins are accommodated. This is illustrated by the fact that φEL is capable of folding β-galactosidase, a 116-kDa protein. Collectively, the architecture and protein-folding mechanism of the φEL chaperonin are significantly different from those observed in group I and II chaperonins.
AB - Chaperonins are ubiquitous, ATP-dependent protein-folding molecular machines that are essential for all forms of life. Bacteriophage φEL encodes its own chaperonin to presumably fold exceedingly large viral proteins via profoundly different nucleotide-binding conformations. Our structural investigations indicate that ATP likely binds to both rings simultaneously and that a misfolded substrate acts as the trigger for ATP hydrolysis. More importantly, the φEL complex dissociates into two single rings resulting from an evolutionarily altered residue in the highly conserved ATP-binding pocket. Conformational changes also more than double the volume of the single-ring internal chamber such that larger viral proteins are accommodated. This is illustrated by the fact that φEL is capable of folding β-galactosidase, a 116-kDa protein. Collectively, the architecture and protein-folding mechanism of the φEL chaperonin are significantly different from those observed in group I and II chaperonins.
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U2 - 10.1016/j.str.2016.02.006
DO - 10.1016/j.str.2016.02.006
M3 - Article
C2 - 26996960
AN - SCOPUS:84961233787
VL - 24
SP - 537
EP - 546
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 4
ER -