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.
authors.affiliation: Department of Chemistry, University of Texas at El Paso, El Paso, TX 79968, USA.
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Molugu
authors.affiliation: Department of Chemistry, University of Texas at El Paso, El Paso, TX 79968, USA.
authors.forename: Zacariah L
authors.initials: ZL
authors.lastname: Hildenbrand
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
authors.forename: David Gene
authors.initials: DG
authors.lastname: Morgan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sherman
authors.affiliation: Neutron Scattering Science Division, Oak Ridge National Laboratory, C23, Building 7964K, Oak Ridge, TN 37831-6430, USA.
authors.forename: Lilin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Biochemistry, University of Utah, 4100 EEJMRB, Salt Lake City, UT 84112-5650, USA.
authors.forename: Costa
authors.initials: C
authors.lastname: Georgopoulos
authors.affiliation: Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny Pereulok, 19, Moscow 127994, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Sernova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Lidia P
authors.initials: LP
authors.lastname: Kurochkina
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Mesyanzhinov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Miroshnikov
authors.affiliation: Department of Chemistry, University of Texas at El Paso, El Paso, TX 79968, USA. Electronic address: rbernal@utep.edu.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Bernal
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D001435:Bacteriophages / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D018833:Chaperonins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000737:chemistry
chemical_list: D014764:Viral Proteins; D000255:Adenosine Triphosphate; D001616:beta-Galactosidase; D018833:Chaperonins