10.1371/journal.pone.0061765
Valentina Taiakina
Valentina
Taiakina
Adrienne N. Boone
Adrienne
N. Boone
Julia Fux
Julia
Fux
Adriano Senatore
Adriano
Senatore
Danielle Weber-Adrian
Danielle
Weber-Adrian
J. Guy Guillemette
J. Guy
Guillemette
J. David Spafford
J.
David Spafford
The Calmodulin-Binding, Short Linear Motif, NSCaTE Is Conserved in L-Type Channel Ancestors of Vertebrate Cav1.2 and Cav1.3 Channels
Public Library of Science
2013
Biochemistry
proteins
ion channels
Evolutionary biology
Organismal evolution
Animal evolution
genomics
Genome databases
Sequence databases
neuroscience
Cellular neuroscience
proteomics
Proteomic databases
Sequence analysis
linear
nscate
conserved
l-type
ancestors
vertebrate
2013-04-23 02:29:45
Dataset
https://plos.figshare.com/articles/dataset/_The_Calmodulin_Binding_Short_Linear_Motif_NSCaTE_Is_Conserved_in_L_Type_Channel_Ancestors_of_Vertebrate_Cav1_2_and_Cav1_3_Channels_/688985
<div><p>NSCaTE is a short linear motif of (x<u>W</u>xxx(<u>I or L</u>)xxxx), composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM) which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca<sup>2+</sup> concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Ca<sub>v</sub>1.1 and Ca<sub>v</sub>1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCa<sub>v</sub>1 from pond snail <i>Lymnaea stagnalis</i> has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA), but disappears in high buffer conditions (10 mM EGTA). Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca<sup>2+</sup>-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels.</p> </div>