Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding

Abstract Proline cis-trans isomerisation is a regulatory mechanism used in a range of biological processes, and is related to various diseases such as Alzheimers disease and cancer. However, the details of the exact molecular mechanism by which it occurs are not known. Using X-ray crystallography, p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Keiko Shinoda, Hideaki Fujitani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ebbfd9e9646472b88ed159160503da8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2ebbfd9e9646472b88ed159160503da8
record_format	dspace
spelling	oai:doaj.org-article:2ebbfd9e9646472b88ed159160503da82021-12-02T15:06:10ZInitiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding10.1038/s41598-017-16766-82045-2322https://doaj.org/article/2ebbfd9e9646472b88ed159160503da82017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16766-8https://doaj.org/toc/2045-2322Abstract Proline cis-trans isomerisation is a regulatory mechanism used in a range of biological processes, and is related to various diseases such as Alzheimers disease and cancer. However, the details of the exact molecular mechanism by which it occurs are not known. Using X-ray crystallography, proline isomerisation has been shown to occur following formation of an antigen-antibody complex between the target epiregulin (EPR) and the antibody 9E5, at proline (Pro103), located in the third complementarity-determining region (CDR) of the heavy chain of 9E5. To obtain an accurate description of the pathway involved in cis-trans isomerisation in this system, we performed ten independent long molecular dynamics (MD) simulations starting at a stable transient bound structure obtained from many short binding MD simulations. As a result, we were able to describe the process by which cis-trans isomerisation is initiated, and suggest a catalysis mechanism for cis-trans isomerization in this antigen-antibody system. We found that Asp102, which is immediately adjacent to Pro103, rotates while changing its interacting partner residues in the light chain of 9E5, and at the same time EPR polar residues help to stabilise the intermediate states in the isomerisation process by interacting strongly with Asp102.Keiko ShinodaHideaki FujitaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keiko Shinoda Hideaki Fujitani Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
description	Abstract Proline cis-trans isomerisation is a regulatory mechanism used in a range of biological processes, and is related to various diseases such as Alzheimers disease and cancer. However, the details of the exact molecular mechanism by which it occurs are not known. Using X-ray crystallography, proline isomerisation has been shown to occur following formation of an antigen-antibody complex between the target epiregulin (EPR) and the antibody 9E5, at proline (Pro103), located in the third complementarity-determining region (CDR) of the heavy chain of 9E5. To obtain an accurate description of the pathway involved in cis-trans isomerisation in this system, we performed ten independent long molecular dynamics (MD) simulations starting at a stable transient bound structure obtained from many short binding MD simulations. As a result, we were able to describe the process by which cis-trans isomerisation is initiated, and suggest a catalysis mechanism for cis-trans isomerization in this antigen-antibody system. We found that Asp102, which is immediately adjacent to Pro103, rotates while changing its interacting partner residues in the light chain of 9E5, and at the same time EPR polar residues help to stabilise the intermediate states in the isomerisation process by interacting strongly with Asp102.
format	article
author	Keiko Shinoda Hideaki Fujitani
author_facet	Keiko Shinoda Hideaki Fujitani
author_sort	Keiko Shinoda
title	Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
title_short	Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
title_full	Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
title_fullStr	Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
title_full_unstemmed	Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
title_sort	initiation of prolyl cis-trans isomerisation in the cdr-h3 loop of an antibody in response to antigen binding
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2ebbfd9e9646472b88ed159160503da8
work_keys_str_mv	AT keikoshinoda initiationofprolylcistransisomerisationinthecdrh3loopofanantibodyinresponsetoantigenbinding AT hideakifujitani initiationofprolylcistransisomerisationinthecdrh3loopofanantibodyinresponsetoantigenbinding
_version_	1718388569227132928

Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding

Ejemplares similares