NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.

Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process req...

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Autores principales:	Roberta Spadaccini, Carmine Ercole, Maria A Gentile, Domenico Sanfelice, Rolf Boelens, Rainer Wechselberger, Gyula Batta, Andrea Bernini, Neri Niccolai, Delia Picone
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d88c0885ac7e46de8a51d8d34b4ea61c
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spelling	oai:doaj.org-article:d88c0885ac7e46de8a51d8d34b4ea61c2021-11-18T07:30:23ZNMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.1932-620310.1371/journal.pone.0029076https://doaj.org/article/d88c0885ac7e46de8a51d8d34b4ea61c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253705/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges.Roberta SpadacciniCarmine ErcoleMaria A GentileDomenico SanfeliceRolf BoelensRainer WechselbergerGyula BattaAndrea BerniniNeri NiccolaiDelia PiconePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29076 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roberta Spadaccini Carmine Ercole Maria A Gentile Domenico Sanfelice Rolf Boelens Rainer Wechselberger Gyula Batta Andrea Bernini Neri Niccolai Delia Picone NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
description	Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges.
format	article
author	Roberta Spadaccini Carmine Ercole Maria A Gentile Domenico Sanfelice Rolf Boelens Rainer Wechselberger Gyula Batta Andrea Bernini Neri Niccolai Delia Picone
author_facet	Roberta Spadaccini Carmine Ercole Maria A Gentile Domenico Sanfelice Rolf Boelens Rainer Wechselberger Gyula Batta Andrea Bernini Neri Niccolai Delia Picone
author_sort	Roberta Spadaccini
title	NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
title_short	NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
title_full	NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
title_fullStr	NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
title_full_unstemmed	NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.
title_sort	nmr studies on structure and dynamics of the monomeric derivative of bs-rnase: new insights for 3d domain swapping.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d88c0885ac7e46de8a51d8d34b4ea61c
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NMR studies on structure and dynamics of the monomeric derivative of BS-RNase: new insights for 3D domain swapping.

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