scholarly journals Tissue-Specificity of Dystrophin–Actin Interactions: Isoform-Specific Thermodynamic Stability and Actin-Binding Function of Tandem Calponin-Homology Domains

ACS Omega ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. 2159-2168
Author(s):  
Vaibhav Upadhyay ◽  
Swati Bandi ◽  
Sudipta Panja ◽  
Laura Saba ◽  
Krishna M. G. Mallela
Keyword(s):  
Thermodynamic Stability ◽  
Tissue Specificity ◽  
Actin Binding ◽  
Calponin Homology ◽  
Binding Function ◽  
Homology Domains

scholarly journals Tug-Of-War Between Thermodynamic Stability and Actin-Binding Function of Tandem Calponin-Homology Domains

2014 ◽  
Vol 106 (2) ◽  
pp. 467a-468a
Author(s):  
Swati Bandi ◽  
Surinder Singh ◽  
Geoffrey Armstrong ◽  
Krishna Mallela
Keyword(s):  
Thermodynamic Stability ◽  
Actin Binding ◽  
Calponin Homology ◽  
Binding Function ◽  
Homology Domains

Abstract 42: Differential Contribution Of The N- And C-terminal Domains To The Folding And Function Of Tandem Calponin-homology Domains

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Krishna Mallela ◽  
Swati Bandi ◽  
Surinder Singh ◽  
Geoffrey Armstrong
Keyword(s):  
Full Length ◽  
Actin Binding ◽  
Main Function ◽  
Calponin Homology ◽  
Terminal Domain ◽  
Binding Domains ◽  
Binding Function ◽  
Ch2 Domain ◽  
The Stability ◽  
And Function

Tandem calponin-homology (CH) domains constitute a major class of actin-binding domains that include dystrophin and utrophin, the two key proteins involved in muscular dystrophy. Despite their importance, how their structure controls their function is not understood. Here, we study the contribution of individual CH domains to the actin-binding function and thermodynamic stability of utrophin’s tandem CH domain. Traditional actin co-sedimentation assays indicate that the isolated C-terminal CH2 domain binds weakly to F-actin when compared with the full-length tandem CH domain. In contrast, isolated CH1 binds to F-actin with a similar efficiency as that of the full-length tandem CH domain. Thus, the obvious question that arises is why tandem CH domains require CH2, when their actin-binding efficiency is originating primarily from CH1. To answer, we probed the thermodynamic stabilities of individual CH domains. Isolated CH1 domain is unstable and is prone to serious aggregation. Isolated CH2 is very stable, even appears to be more stable than the full-length tandem CH domain. In addition, the CH2 domain, which is more stable, is less functional. These results indicate that the main function of CH2 is to stabilize CH1. Consistently, the proposed structure of utrophin’s tandem CH domain based on earlier X-ray studies indicates a close proximity between the C-terminal helix of CH2 and the N-terminal helix of CH1, and this helix in CH2 is more dynamic in the full-length protein when compared with that in the absence of CH1, suggesting the mechanism by which CH2 stabilizes CH1. These observations indicate that the two CH domains contribute differentially to the folding and function of tandem CH domains, although both domains essentially have the same native structure in the tandem CH domain. The N-terminal domain determines the function, whereas the C-terminal domain determines the stability. This work was funded by the AHA Grant 11SDG4880046.

Novel structural insights into F-actin-binding and novel functions of calponin homology domains

2008 ◽  
Vol 18 (6) ◽  
pp. 702-708 ◽  
Author(s):  
Björn Sjöblom ◽  
Jari Ylänne ◽  
Kristina Djinović-Carugo
Keyword(s):  
Actin Binding ◽  
Calponin Homology ◽  
Structural Insights ◽  
Homology Domains

scholarly journals Single calponin homology domains are not actin-binding domains

1998 ◽  
Vol 8 (19) ◽  
pp. R673-R675 ◽  
Author(s):  
Mario Gimona ◽  
Steven J. Winder
Keyword(s):  
Actin Binding ◽  
Calponin Homology ◽  
Binding Domains ◽  
Homology Domains

scholarly journals Structural comparisons of calponin homology domains: implications for actin binding

Structure ◽  
1998 ◽  
Vol 6 (11) ◽  
pp. 1419-1431 ◽  
Author(s):  
Sonia Bañuelos ◽  
Matti Saraste ◽  
Kristina Djinović Carugo
Keyword(s):  
Actin Binding ◽  
Calponin Homology ◽  
Homology Domains

scholarly journals Large-scale opening of utrophin's tandem calponin homology (CH) domains upon actin binding by an induced-fit mechanism

2011 ◽  
Vol 108 (31) ◽  
pp. 12729-12733 ◽  
Author(s):  
A. Y. Lin ◽  
E. Prochniewicz ◽  
Z. M. James ◽  
B. Svensson ◽  
D. D. Thomas
Keyword(s):  
Large Scale ◽  
Actin Binding ◽  
Induced Fit ◽  
Calponin Homology

Expression of calmin, a novel developmentally regulated brain protein with calponin-homology domains

2003 ◽  
Vol 112 (1-2) ◽  
pp. 146-152 ◽  
Author(s):  
Mikiro Takaishi ◽  
Zenji Ishisaki ◽  
Toshiko Yoshida ◽  
Yoshimi Takata ◽  
Nam-ho Huh
Keyword(s):  
Brain Protein ◽  
Developmentally Regulated ◽  
Calponin Homology ◽  
Homology Domains

scholarly journals Phosphorylation-dependent Conformational Changes Induce a Switch in the Actin-binding Function of MARCKS

1999 ◽  
Vol 274 (51) ◽  
pp. 36472-36478 ◽  
Author(s):  
Michael R. Bubb ◽  
Robert H. Lenox ◽  
Arthur S. Edison
Keyword(s):  
Conformational Changes ◽  
Actin Binding ◽  
Binding Function

scholarly journals Extracellular regulated kinase (ERK) interaction with actin and the calponin homology (CH) domain of actin-binding proteins

1999 ◽  
Vol 344 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Barbara D. LEINWEBER ◽  
Paul C. LEAVIS ◽  
Zenon GRABAREK ◽  
C.-L. Albert WANG ◽  
Kathleen G. MORGAN
Keyword(s):  
Binding Site ◽  
Potential Function ◽  
Binding Proteins ◽  
Actin Binding ◽  
Actin Binding Proteins ◽  
Calponin Homology ◽  
Signalling Molecule ◽  
Fluorescence Change ◽  
Extracellular Regulated Kinase ◽  
Overlay Assay

An interaction between extracellular regulated kinase 1 (ERK1) and calponin has previously been reported (Menice, Hulvershorn, Adam, Wang and Morgan (1997) J. Biol. Chem.272(40), 25157-25161) and has been suggested to reflect a function of calponin as a signalling molecule. We report in this study that calponin binds to both ERK1 and ERK2 under native conditions as well as in an overlay assay. Using chymotryptic fragments of calponin, the binding site of ERK on calponin was identified as the calponin homology (CH) domain, an N-terminal region of calponin found in other actin-binding proteins. ERK also bound, in a gel overlay assay, α-actinin, a protein with two tandem CH domains, as well as a 27 kDa thermolysin product of α-actinin containing the CH domains of α-actinin. The CH domain of calponin could compete with intact calponin or α-actinin for ERK binding. Titration of acrylodan-labelled calponin with ERK gave a Ka of 6×106 M-1 and titration of acrylodan-labelled calponin with a peptide from the αL16 helix of ERK gave a Ka of 1×106 M-1. Recombinant ERK was found to co-sediment with purified actin and induced a fluorescence change in pyrene-labelled F-actin (Ka = 5×106 M-1). The interaction of ERK with CH domains points to a new potential function for CH domains. The interaction of ERK with actin raises the possibility that actin may provide a scaffold for ERK signalling complexes in both muscle and non-muscle cells.

Sign in / Sign up

Export Citation Format

Share Document