Direct visualization of protease action on collagen triple helical structure.

Enzymatic processing of extracellular matrix (ECM) macromolecules by matrix metalloproteases (MMPs) is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant informati...

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Autores principales:	Gabriel Rosenblum, Philippe E Van den Steen, Sidney R Cohen, Arkady Bitler, David D Brand, Ghislain Opdenakker, Irit Sagi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e71aeca16b1d4383a579ce21a040cd4e
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spelling	oai:doaj.org-article:e71aeca16b1d4383a579ce21a040cd4e2021-12-02T20:20:46ZDirect visualization of protease action on collagen triple helical structure.1932-620310.1371/journal.pone.0011043https://doaj.org/article/e71aeca16b1d4383a579ce21a040cd4e2010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20585385/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Enzymatic processing of extracellular matrix (ECM) macromolecules by matrix metalloproteases (MMPs) is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant information is available on the mode by which matrix proteases degrade ECM substrates. An example is the enzymatic degradation of triple helical collagen II fragments, generated by the collagenase MMP-8 cleavage, during the course of acute inflammatory conditions by gelatinase B/MMP-9. As is the case for many other matrix proteases, it is not clear how MMP-9 recognizes, binds and digests collagen in this important physiological process. We used single molecule imaging to directly visualize this protease during its interaction with collagen fragments. We show that the initial binding is mediated by the diffusion of the protease along the ordered helix on the collagen (3/4) fragment, with preferential binding of the collagen tail. As the reaction progressed and prior to collagen degradation, gelatin-like morphologies resulting from the denaturation of the triple helical collagen were observed. Remarkably, this activity was independent of enzyme proteolysis and was accompanied by significant conformational changes of the working protease. Here we provide the first direct visualization of highly complex mechanisms of macromolecular interactions governing the enzymatic processing of ECM substrates by physiological protease.Gabriel RosenblumPhilippe E Van den SteenSidney R CohenArkady BitlerDavid D BrandGhislain OpdenakkerIrit SagiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e11043 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gabriel Rosenblum Philippe E Van den Steen Sidney R Cohen Arkady Bitler David D Brand Ghislain Opdenakker Irit Sagi Direct visualization of protease action on collagen triple helical structure.
description	Enzymatic processing of extracellular matrix (ECM) macromolecules by matrix metalloproteases (MMPs) is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant information is available on the mode by which matrix proteases degrade ECM substrates. An example is the enzymatic degradation of triple helical collagen II fragments, generated by the collagenase MMP-8 cleavage, during the course of acute inflammatory conditions by gelatinase B/MMP-9. As is the case for many other matrix proteases, it is not clear how MMP-9 recognizes, binds and digests collagen in this important physiological process. We used single molecule imaging to directly visualize this protease during its interaction with collagen fragments. We show that the initial binding is mediated by the diffusion of the protease along the ordered helix on the collagen (3/4) fragment, with preferential binding of the collagen tail. As the reaction progressed and prior to collagen degradation, gelatin-like morphologies resulting from the denaturation of the triple helical collagen were observed. Remarkably, this activity was independent of enzyme proteolysis and was accompanied by significant conformational changes of the working protease. Here we provide the first direct visualization of highly complex mechanisms of macromolecular interactions governing the enzymatic processing of ECM substrates by physiological protease.
format	article
author	Gabriel Rosenblum Philippe E Van den Steen Sidney R Cohen Arkady Bitler David D Brand Ghislain Opdenakker Irit Sagi
author_facet	Gabriel Rosenblum Philippe E Van den Steen Sidney R Cohen Arkady Bitler David D Brand Ghislain Opdenakker Irit Sagi
author_sort	Gabriel Rosenblum
title	Direct visualization of protease action on collagen triple helical structure.
title_short	Direct visualization of protease action on collagen triple helical structure.
title_full	Direct visualization of protease action on collagen triple helical structure.
title_fullStr	Direct visualization of protease action on collagen triple helical structure.
title_full_unstemmed	Direct visualization of protease action on collagen triple helical structure.
title_sort	direct visualization of protease action on collagen triple helical structure.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/e71aeca16b1d4383a579ce21a040cd4e
work_keys_str_mv	AT gabrielrosenblum directvisualizationofproteaseactiononcollagentriplehelicalstructure AT philippeevandensteen directvisualizationofproteaseactiononcollagentriplehelicalstructure AT sidneyrcohen directvisualizationofproteaseactiononcollagentriplehelicalstructure AT arkadybitler directvisualizationofproteaseactiononcollagentriplehelicalstructure AT daviddbrand directvisualizationofproteaseactiononcollagentriplehelicalstructure AT ghislainopdenakker directvisualizationofproteaseactiononcollagentriplehelicalstructure AT iritsagi directvisualizationofproteaseactiononcollagentriplehelicalstructure
_version_	1718374200159240192

Direct visualization of protease action on collagen triple helical structure.

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