Forced Unfolding Modulated by Disulfide Bonds in the Immunoglobulin Domains of the Cell Adhesion Molecule Mel-CAM.
(2001) In Proceedings of the National Academy of Sciences 98(4). p.1565-1570- Abstract
- Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains intradomain disulfide bonds. The Ig domains of all such CAMs have conformations homologous to cadherin extracellular domains, titin Ig-type domains, and fibronectin type-III (FNIII) domains. Atomic force microscopy has been used to extend the five Ig domains of Mel-CAM (melanoma CAM)---a protein that is overexpressed in metastatic melanomas---under conditions where the disulfide bonds were either left intact or disrupted through reduction. Under physiological conditions where intradomain disulfide bonds are intact, partial unfolding was observed... (More)
- Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains intradomain disulfide bonds. The Ig domains of all such CAMs have conformations homologous to cadherin extracellular domains, titin Ig-type domains, and fibronectin type-III (FNIII) domains. Atomic force microscopy has been used to extend the five Ig domains of Mel-CAM (melanoma CAM)---a protein that is overexpressed in metastatic melanomas---under conditions where the disulfide bonds were either left intact or disrupted through reduction. Under physiological conditions where intradomain disulfide bonds are intact, partial unfolding was observed at forces far smaller than those reported previously for either titin's Ig-type domains or tenascin's FNIII domains. This partial unfolding under low force may be an important mechanism for imparting elasticity to cell-cell contacts, as well as a regulatory mechanism for adhesive interactions. Under reducing conditions, Mel-CAM's Ig domains were found to fully unfold through a partially folded state and at slightly higher forces. The results suggest that, in divergent evolution of all such domains, stabilization imparted by disulfide bonds relaxes requirements for strong, noncovalent, folded-state interactions. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1118092
- author
- Carl, Pilippe. ; Kwok, Carol. ; Manderson, Gavin LU ; Speicher, David W. and Discher, Dennis E
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 98
- issue
- 4
- pages
- 1565 - 1570
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:0035852740
- pmid:11171991
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.031409698
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)
- id
- 010b7b0e-865f-4222-be8f-b8ccf6b1f9fd (old id 1118092)
- date added to LUP
- 2016-04-01 12:36:30
- date last changed
- 2022-01-27 07:22:58
@article{010b7b0e-865f-4222-be8f-b8ccf6b1f9fd,
abstract = {{Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains intradomain disulfide bonds. The Ig domains of all such CAMs have conformations homologous to cadherin extracellular domains, titin Ig-type domains, and fibronectin type-III (FNIII) domains. Atomic force microscopy has been used to extend the five Ig domains of Mel-CAM (melanoma CAM)---a protein that is overexpressed in metastatic melanomas---under conditions where the disulfide bonds were either left intact or disrupted through reduction. Under physiological conditions where intradomain disulfide bonds are intact, partial unfolding was observed at forces far smaller than those reported previously for either titin's Ig-type domains or tenascin's FNIII domains. This partial unfolding under low force may be an important mechanism for imparting elasticity to cell-cell contacts, as well as a regulatory mechanism for adhesive interactions. Under reducing conditions, Mel-CAM's Ig domains were found to fully unfold through a partially folded state and at slightly higher forces. The results suggest that, in divergent evolution of all such domains, stabilization imparted by disulfide bonds relaxes requirements for strong, noncovalent, folded-state interactions.}},
author = {{Carl, Pilippe. and Kwok, Carol. and Manderson, Gavin and Speicher, David W. and Discher, Dennis E}},
issn = {{1091-6490}},
language = {{eng}},
number = {{4}},
pages = {{1565--1570}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Forced Unfolding Modulated by Disulfide Bonds in the Immunoglobulin Domains of the Cell Adhesion Molecule Mel-CAM.}},
url = {{http://dx.doi.org/10.1073/pnas.031409698}},
doi = {{10.1073/pnas.031409698}},
volume = {{98}},
year = {{2001}},
}