The Differential Response to Ca<sup>2+</sup> from
Vertebrate and Invertebrate Calumenin Is Governed by a Single Amino
Acid Residue
Sasirekha Narayanasamy
Gopala Krishna Aradhyam
10.1021/acs.biochem.7b00762.s001
https://acs.figshare.com/articles/journal_contribution/The_Differential_Response_to_Ca_sup_2_sup_from_Vertebrate_and_Invertebrate_Calumenin_Is_Governed_by_a_Single_Amino_Acid_Residue/5820996
Calumenin
(Calu) is a well-conserved multi-EF-hand-containing Ca<sup>2+</sup>-binding protein. In this work, we focused on the alterations
that calumenin has undergone during evolution. We demonstrate that
vertebrate calumenin is significantly different from its invertebrate
homologues with respect to its response to Ca<sup>2+</sup> binding.
Human calumenin (HsCalu1) is intrinsically unstructured in the Ca<sup>2+</sup> free form and responds to Ca<sup>2+</sup> with a dramatic
gain in structure. Calumenin from <i>Caenorhabditis elegans</i> (CeCalu) is structured even in the apo form, with no conformational
change upon binding of Ca<sup>2+</sup>. We decode this structural
and functional distinction by identifying a single “Leu”
residue-based switch located in the fourth EF-hand of HsCalu1, occupied
by “Gly” in the invertebrate homologues. We demonstrate
that replacing Leu with Gly (L150G) in HsCalu1 enables the protein
to adopt a structural fold even in the Ca<sup>2+</sup> free form,
similar to CeCalu, leading to ligand compensation (adoption of structure
in the absence of Ca<sup>2+</sup>). The fourth (of seven) EF-hand
of HsCalu1 nucleates the structural fold of the protein depending
on the switch residue (Gly or Leu). Our analyses reveal that the Leu
that replaced Gly from fishes onward is absolutely conserved in higher
vertebrates, while lower organisms have Gly, not only enlarging the
scope of Ca<sup>2+</sup>-dependent structural transitions but also
drawing a boundary between the invertebrate and vertebrate calumenin.
The evolutionary selection of the switch residue strongly corroborates
the change in the structure of the protein and its pleiotropic functions
and seems like it can be extended to the presence or absence of a
heart in that organism.
2018-01-10 00:00:00
EF-hand
CeCalu
absence
Calumenin
Leu
invertebrate homologues
Gly
switch residue
150G
binding
calumenin
protein
HsCalu 1 nucleates
organism