Change search
Link to record
Permanent link

Direct link
BETA
Westerlund, Annie M.ORCID iD iconorcid.org/0000-0003-2288-5711
Publications (3 of 3) Show all publications
Westerlund, A. M. & Delemotte, L. (2018). Effect of Ca2+on the promiscuous target-protein binding of calmodulin. PloS Computational Biology, 14(4), Article ID e1006072.
Open this publication in new window or tab >>Effect of Ca2+on the promiscuous target-protein binding of calmodulin
2018 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 14, no 4, article id e1006072Article in journal (Refereed) Published
Abstract [en]

Calmodulin (CaM) is a calcium sensing protein that regulates the function of a large number of proteins, thus playing a crucial part in many cell signaling pathways. CaM has the ability to bind more than 300 different target peptides in a Ca2+-dependent manner, mainly through the exposure of hydrophobic residues. How CaM can bind a large number of targets while retaining some selectivity is a fascinating open question. Here, we explore the mechanism of CaM selective promiscuity for selected target proteins. Analyzing enhanced sampling molecular dynamics simulations of Ca2+-bound and Ca2+-free CaM via spectral clustering has allowed us to identify distinct conformational states, characterized by interhelical angles, secondary structure determinants and the solvent exposure of specific residues. We searched for indicators of conformational selection by mapping solvent exposure of residues in these conformational states to contacts in structures of CaM/target peptide complexes. We thereby identified CaM states involved in various binding classes arranged along a depth binding gradient. Binding Ca2+modifies the accessible hydrophobic surface of the two lobes and allows for deeper binding. Apo CaM indeed shows shallow binding involving predominantly polar and charged residues. Furthermore, binding to the C-terminal lobe of CaM appears selective and involves specific conformational states that can facilitate deep binding to target proteins, while binding to the N-terminal lobe appears to happen through a more flexible mechanism. Thus the long-ranged electrostatic interactions of the charged residues of the N-terminal lobe of CaM may initiate binding, while the short-ranged interactions of hydrophobic residues in the C-terminal lobe of CaM may account for selectivity. This work furthers our understanding of the mechanism of CaM binding and selectivity to different target proteins and paves the way towards a comprehensive model of CaM selectivity.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:kth:diva-228941 (URN)10.1371/journal.pcbi.1006072 (DOI)000432169600018 ()29614072 (PubMedID)2-s2.0-85046377207 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180530

Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2018-09-12Bibliographically approved
Westerlund, A. M., Harpole, T. J., Blau, C. & Delemotte, L. (2018). Inference of Calmodulin's Ca2+: Dependent Free Energy Landscapes via Gaussian Mixture Model Validation. Paper presented at 62nd Annual Meeting of the Biophysical-Society, FEB 17-21, 2018, San Francisco, CA. Biophysical Journal, 114(3), 675A-675A
Open this publication in new window or tab >>Inference of Calmodulin's Ca2+: Dependent Free Energy Landscapes via Gaussian Mixture Model Validation
2018 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 3, p. 675A-675AArticle in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
CELL PRESS, 2018
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-227240 (URN)10.1016/j.bpj.2017.11.3640 (DOI)000430563300366 ()
Conference
62nd Annual Meeting of the Biophysical-Society, FEB 17-21, 2018, San Francisco, CA
Note

QC 20180518

Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2019-08-20Bibliographically approved
Westerlund, A. M. & Delemotte, L. (2018). On the Selective Promiscuity of Calmodulin. Paper presented at 62nd Annual Meeting of the Biophysical-Society, FEB 17-21, 2018, San Francisco, CA. Biophysical Journal, 114(3), 7A-8A
Open this publication in new window or tab >>On the Selective Promiscuity of Calmodulin
2018 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 3, p. 7A-8AArticle in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
CELL PRESS, 2018
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-227241 (URN)10.1016/j.bpj.2017.11.076 (DOI)000429315800042 ()
Conference
62nd Annual Meeting of the Biophysical-Society, FEB 17-21, 2018, San Francisco, CA
Note

QC 20180517

Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-05-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2288-5711

Search in DiVA

Show all publications