IndraLab

"The 3 calmodulin genes ( CALM1-3 ) were scored separately but discussed as a group because they all encode for an identical protein. xref CALM1 and CALM2 were first associated with LQTS by exome sequencing of 2 unrelated infants with QT prolongation where de novo variants were identified. xref Subsequent studies uncovered further genetic evidence for these genes, including CALM3. xref – xref Most recently, the International Calmodulinopthy Registry has published a series of 36 LQTS cases secondary to rare variants distributed among all 3 CALM genes. xref In all cases identified, no other family members were found to be phenotype-positive and were thus concordant with de novo variants, although not in all families was this proven by sequencing of both parents and confirmation of paternity."

"CaM1 Binds to the CaM N-lobe and CaM2 Binds to the CaM C-lobe.."

"CaM binding decreases the CNG channel-binding affinity for cGMP and causes decreased Ca 2+ influx. xref , xref Two CaM-binding sites are located in CNGB1 called CaM1 (residues 565–589) and CaM2 (residues 1120–1147) ( xref ). xref , xref , xref CaM1 is required for Ca 2+ -dependent modulation of the CNGA1/CNGB1 heteromeric channels. xref , xref The function of CaM2 is not known, but CaM2 is located adjacent to the CNBD where it could affect ligand binding. xref A recent cryoEM structure of the retinal CNG channel revealed that a helix within CNGB1 is bound to the C-terminal domain of CaM (residues 80–149, called the C-lobe). xref However, the cryoEM structure lacked sufficient resolution to distinguish whether the CaM C-lobe is bound to CaM1 or CaM2, and the CaM N-lobe (residues 1–80) was completely missing in the structure."

"The efficiency of these tools facilitated analysis of the functions of the essential CaM3 gene as well as the synthetic lethal interaction between CaM1 and CaM2 ."

"Ca 2+ -free CaM Exhibits Very Weak Binding to CaM1 and CaM2."

"Peptide fragments of CaM1 (residues 565–589) and CaM2 (residues 1120–1147) were shown previously to bind to Ca 2+ -bound CaM, xref , xref but the binding of CaM1 and CaM2 to Ca 2+ -free CaM has not been reported."

"Ca 2+ -free CaM (apoCaM) exhibits very weak binding to CaM1 or CaM2 that is likely not physiologically relevant."

"Alternatively, a single CaM might bind to one CNGB1 if the two CaM lobes (from a single CaM) each bind separately to CaM1 and CaM2."

"Interestingly, a difference in fluorescence amplitudes between Cam1 and Cam2 binding to the IQ12 motif indicated an impact upon the conformation of the lever arm (Figure 2G), providing a potential mechanism to control Myo1 motor activity directly."

"Peptide fragments of CaM1 (residues 565–589) and CaM2 (residues 1120–1147) were shown previously to bind to Ca -bound CaM, but the binding of CaM1 and CaM2 to Ca -free CaM has not been reported."

No evidence text available