Sequestration of Ribosome during Protein Aggregate Formation: Contribution of ribosomal RNA.
An understanding of the mechanisms underlying protein aggregation and cytotoxicity of the protein aggregates is crucial in the prevention of several diseases in humans. Ribosome, the cellular protein synthesis machine is capable of acting as a protein folding modulator. The peptidyltransferase center residing in the domain V of large ribosomal subunit 23S rRNA is the centre for the protein folding ability of the ribosome and is also the cellular target of several antiprion compounds. Our in vitro studies unexpectedly reveal that the partial unfolding or aggregation of lysozyme under reducing conditions in presence of the ribosome can induce aggregation of ribosomal components. Electrostatic interactions complemented by specific rRNA-protein interaction drive the ribosome-protein aggregation process. Under similar conditions the rRNA, especially the large subunit rRNA and in vitro transcribed RNA corresponding to domain V of 23S rRNA (bDV RNA) stimulates lysozyme aggregation leading to RNA-protein aggregate formation. Protein aggregation during the refolding of non-disulfide containing protein BCAII at high concentrations also induces ribosome aggregation. BCAII aggregation was also stimulated in presence of the large subunit rRNA. Our observations imply that the specific sequestration of the translation machine by aggregating proteins might contribute to their cytotoxicity.
Structural Biology &Bio-Informatics Division, Indian Institute of Chemical Biology (Council of Scientific &Industrial Research), 4, Raja S.C. Mullick Road, Kolkata, 700 032, India.
Bani K
BK
Pathak
Krish Biotech Research Pvt. Ltd. T-1, QK-17 (Part) WBIIDC, Kalyani, Phase III, Nadia West Bengal 741 235, India.
Surojit
S
Mondal
Department of Biotechnology, St. Xavier's College, Park Street, Kolkata-700016, West Bengal, India.
Senjuti
S
Banerjee
National Institute of Cholera and Enteric Diseases P-33, C.I.T. Road, Scheme XM, Beleghata, India.
Amar Nath
AN
Ghosh
Department of Biotechnology, St. Xavier's College, Park Street, Kolkata-700016, West Bengal, India.
Chandana
C
Barat
D000818:Animals; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002645:Chickens; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000235:genetics* / Q000378:metabolism; D066329:Protein Aggregates / Q000235:genetics*; D014176:Protein Biosynthesis; D017510:Protein Folding; D058767:Protein Unfolding; D012338:RNA, Ribosomal, 23S / Q000235:genetics* / Q000378:metabolism; D054681:Ribosome Subunits, Large, Bacterial / Q000201:enzymology / Q000235:genetics*; D055672:Static Electricity
D066329:Protein Aggregates; D012338:RNA, Ribosomal, 23S; D006493:Heparin; D010458:Peptidyl Transferases; D009113:Muramidase; D024402:Carbonic Anhydrase II