Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin

Sudheer K. Molugu; Zacariah L. Hildenbrand; David Gene Morgan; Michael B. Sherman; Lilin He; Costa Georgopoulos; Natalia V. Sernova; Lidia P. Kurochkina; Vadim V. Mesyanzhinov; Konstantin A. Miroshnikov; Ricardo A. Bernal

doi:10.1016/j.str.2016.02.006

Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin

Sudheer K. Molugu, Zacariah L. Hildenbrand, David Gene Morgan, Michael B. Sherman, Lilin He, Costa Georgopoulos, Natalia V. Sernova, Lidia P. Kurochkina, Vadim V. Mesyanzhinov, Konstantin A. Miroshnikov, Ricardo A. Bernal

SANS & Spin Echo

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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
Pages (from-to)	537-546
Number of pages	10
Journal	Structure
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2016.02.006
State	Published - Apr 5 2016

Funding

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.

Funders	Funder number
Center for Structural Molecular Biology	FWP ERKP291
Scientific User Facilities Division
National Science Foundation	MRI 0923437
National Institutes of Health
U.S. Department of Energy
National Institute of General Medical Sciences	SC3GM113805
Welch Foundation	AH–1649
Basic Energy Sciences
Biological and Environmental Research
Oak Ridge National Laboratory
Russian Foundation for Basic Research	11-04-00935

Access to Document

10.1016/j.str.2016.02.006

Cite this

@article{e515de10d3a34271a066043df189f101,

title = "Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin",

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.",

author = "Molugu, {Sudheer K.} and Hildenbrand, {Zacariah L.} and Morgan, {David Gene} and Sherman, {Michael B.} and Lilin He and Costa Georgopoulos and Sernova, {Natalia V.} and Kurochkina, {Lidia P.} and Mesyanzhinov, {Vadim V.} and Miroshnikov, {Konstantin A.} and Bernal, {Ricardo A.}",

year = "2016",

month = apr,

day = "5",

doi = "10.1016/j.str.2016.02.006",

language = "English",

volume = "24",

pages = "537--546",

journal = "Structure",

issn = "0969-2126",

publisher = "Elsevier",

number = "4",

}

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.

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

U2 - 10.1016/j.str.2016.02.006

DO - 10.1016/j.str.2016.02.006

M3 - Article

C2 - 26996960

AN - SCOPUS:84961233787

SN - 0969-2126

VL - 24

SP - 537

EP - 546

JO - Structure

JF - Structure

IS - 4

ER -

Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL-Encoded Chaperonin

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this