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

Journal Article · Thu Mar 17 04:00:00 EDT 2016 · Structure

DOI:https://doi.org/10.1016/j.str.2016.02.006· OSTI ID:1352746

Molugu, Sudheer  K. ^[1]; Hildenbrand, Zacariah L. ^[1]; Morgan, David Gene ^[2]; Sherman, Michael B. ^[3]; He, Lilin ^[4]; Georgopoulos, Costa ^[5]; Sernova, Natalia V. ^[6]; Kurochkina, Lidia P. ^[7]; Mesyanzhinov, Vadim V. ^[7]; Miroshnikov, Konstantin A. ^[7]; Bernal, Ricardo A. ^[1]

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1. Univ. of Texas, El Paso, TX (United States). Department of Chemistry
2. Indiana Univ., Bloomington, IN (United States). Department of Chemistry
3. University of Texas Medical Branch, Galveston, TX (United States). Department of Biochemistry and Molecular Biology
4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Science Division
5. Univ. of Utah, Salt Lake City, UT (United States). Department of Biochemistry
6. Russian Academy of Sciences, Moscow (Russia). Kharkevich Institute for Information Transmission Problems
7. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow (Russia)

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.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1352746
• Journal Information: Structure, Journal Name: Structure Journal Issue: 4 Vol. 24; ISSN 0969-2126
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES