A Novel Trans Conformation of Ligand-Free Calmodulin

Veerendra Kumar,Vishnu Priyanka Reddy Chichili,J. Sivaraman,Xuhua Tang,Narayanaswamy Srinivasan

doi:10.1371/journal.pone.0054834

Veerendra Kumar, Vishnu Priyanka Reddy Chichili + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0054834

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Journal: PloS one	Publication Date: Jan 29, 2013
Citations: 15	License type: CC BY 4.0

Affiliation: National University of Singapore

Abstract

Calmodulin (CaM) is a highly conserved eukaryotic protein that binds specifically to more than 100 target proteins in response to calcium (Ca2+) signal. CaM adopts a considerable degree of structural plasticity to accomplish this physiological role; however, the nature and extent of this plasticity remain to be fully understood. Here, we report the crystal structure of a novel trans conformation of ligand-free CaM where the relative disposition of two lobes of CaM is different, a conformation to-date not reported. While no major structural changes were observed in the independent N- and C-lobes as compared with previously reported structures of Ca2+/CaM, the central helix was tilted by ∼90° at Arg75. This is the first crystal structure of CaM to show a drastic conformational change in the central helix, and reveals one of several possible conformations of CaM to engage with its binding partner.

Highlights

Calmodulin (CaM), a 16.7 kDa protein found in all eukaryotic cells, has been extensively studied as a primary calcium (Ca2+)binding protein [1]
The helices of two EF-hands motifs create a Phe and Met-rich hydrophobic pocket that is exposed to solvent and involved in target binding [5]
The central helix of CaM is highly flexible and is the key to its ability to bind a wide range of targets [9]

Summary

Introduction

Calmodulin (CaM), a 16.7 kDa protein found in all eukaryotic cells, has been extensively studied as a primary calcium (Ca2+)binding protein [1]. CaM consists of two homologous (46% sequence identity) globular lobes; each has a pair of Ca2+ binding sites (EF-hand motifs), connected by a flexible linker [4]. The helices of two EF-hands motifs create a Phe and Met-rich hydrophobic pocket that is exposed to solvent and involved in target binding [5]. Ca2+ induces a large conformational change, exposing the hydrophobic surface and facilitating binding between Ca2+/ CaM and a number of basic amphiphilic helices on target proteins [8]. The central helix of CaM is highly flexible and is the key to its ability to bind a wide range of targets [9]

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