Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 537-546 |
| Number of pages | 10 |
| Journal | Structure |
| Volume | 24 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 5 2016 |
Fingerprint
ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Cite this
Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin. / Molugu, Sudheer K.; Hildenbrand, Zacariah L.; Morgan, David Gene; Sherman, Michael; He, Lilin; Georgopoulos, Costa; Sernova, Natalia V.; Kurochkina, Lidia P.; Mesyanzhinov, Vadim V.; Miroshnikov, Konstantin A.; Bernal, Ricardo A.
In: Structure, Vol. 24, No. 4, 05.04.2016, p. 537-546.Research output: Contribution to journal › Article
}
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
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84961233787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961233787&partnerID=8YFLogxK
U2 - 10.1016/j.str.2016.02.006
DO - 10.1016/j.str.2016.02.006
M3 - Article
VL - 24
SP - 537
EP - 546
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 4
ER -