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Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps
Creatine kinase (CK) is located in an isoenzyme-specific manner at subcellular sites of energy production and consumption. In muscle cells, the muscle-type CK isoform (MM-CK) specifically interacts with the sarcomeric M-line, while the highly homologous brain-type CK isoform (BB-CK) does not share t...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175123/ https://www.ncbi.nlm.nih.gov/pubmed/10851020 |
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author | Hornemann, Thorsten Stolz, Martin Wallimann, Theo |
author_facet | Hornemann, Thorsten Stolz, Martin Wallimann, Theo |
author_sort | Hornemann, Thorsten |
collection | PubMed |
description | Creatine kinase (CK) is located in an isoenzyme-specific manner at subcellular sites of energy production and consumption. In muscle cells, the muscle-type CK isoform (MM-CK) specifically interacts with the sarcomeric M-line, while the highly homologous brain-type CK isoform (BB-CK) does not share this property. Sequence comparison revealed two pairs of lysine residues that are highly conserved in M-CK but are not present in B-CK. The role of these lysines in mediating M-line interaction was tested with a set of M-CK and B-CK point mutants and chimeras. We found that all four lysine residues are involved in the isoenzyme-specific M-line interaction, acting pair-wise as strong (K104/K115) and weak interaction sites (K8/K24). An exchange of these lysines in MM-CK led to a loss of M-line binding, whereas the introduction of the very same lysines into BB-CK led to a gain of function by transforming BB-CK into a fully competent M-line–binding protein. The role of the four lysines in MM-CK is discussed within the context of the recently solved x-ray structures of MM-CK and BB-CK. |
format | Text |
id | pubmed-2175123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21751232008-05-01 Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps Hornemann, Thorsten Stolz, Martin Wallimann, Theo J Cell Biol Original Article Creatine kinase (CK) is located in an isoenzyme-specific manner at subcellular sites of energy production and consumption. In muscle cells, the muscle-type CK isoform (MM-CK) specifically interacts with the sarcomeric M-line, while the highly homologous brain-type CK isoform (BB-CK) does not share this property. Sequence comparison revealed two pairs of lysine residues that are highly conserved in M-CK but are not present in B-CK. The role of these lysines in mediating M-line interaction was tested with a set of M-CK and B-CK point mutants and chimeras. We found that all four lysine residues are involved in the isoenzyme-specific M-line interaction, acting pair-wise as strong (K104/K115) and weak interaction sites (K8/K24). An exchange of these lysines in MM-CK led to a loss of M-line binding, whereas the introduction of the very same lysines into BB-CK led to a gain of function by transforming BB-CK into a fully competent M-line–binding protein. The role of the four lysines in MM-CK is discussed within the context of the recently solved x-ray structures of MM-CK and BB-CK. The Rockefeller University Press 2000-06-12 /pmc/articles/PMC2175123/ /pubmed/10851020 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Hornemann, Thorsten Stolz, Martin Wallimann, Theo Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title | Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title_full | Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title_fullStr | Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title_full_unstemmed | Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title_short | Isoenzyme-Specific Interaction of Muscle-Type Creatine Kinase with the Sarcomeric M-Line Is Mediated by Nh(2)-Terminal Lysine Charge-Clamps |
title_sort | isoenzyme-specific interaction of muscle-type creatine kinase with the sarcomeric m-line is mediated by nh(2)-terminal lysine charge-clamps |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175123/ https://www.ncbi.nlm.nih.gov/pubmed/10851020 |
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