Format

Send to

Choose Destination
See comment in PubMed Commons below
J Am Chem Soc. 2013 Jul 3;135(26):9648-51. doi: 10.1021/ja4051422. Epub 2013 Jun 20.

The length of the calmodulin linker determines the extent of transient interdomain association and target affinity.

Author information

1
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.

Abstract

Calmodulin (CaM), the prototypical calcium sensing protein in eukaryotes, comprises two domains separated by a short flexible linker, which allows CaM to assume a wide range of extended and compact conformations. Here we use NMR relaxation measurements to explore the role of the linker in CaM function and dynamics. Using paramagnetic relaxation enhancement (PRE) measurements, we examine the effect of changes in the length and rigidity of the linker on the transient association between the two domains of Ca(2+)-bound CaM (CaM-4Ca(2+)). We observe that transient interdomain association, represented by an effective molarity (M(eff)), is maximal for a linker extended by one residue from the wild-type length and decreases for lengths longer or shorter than that. The results can be quantitatively rationalized using a simplified model of a random coil whose two ends must be a specific distance apart for an interaction to occur. The results correlate well with the affinity of CaM-4Ca(2+) for a target peptide, suggesting that the transient compact states adopted by CaM-4Ca(2+) in the absence of peptide play a direct role in facilitating target binding.

PMID:
23782151
PMCID:
PMC3748814
DOI:
10.1021/ja4051422
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Support Center