scholarly journals Domain Interaction Footprint: a multi-classification approach to predict domain–peptide interactions

2009 ◽  
Vol 25 (13) ◽  
pp. 1632-1639 ◽  
Author(s):  
Christian Schillinger ◽  
Prisca Boisguerin ◽  
Gerd Krause
Keyword(s):  
Domain Interaction ◽  
Classification Approach ◽  
Peptide Interactions ◽  
Domain Peptide ◽  
Multi Classification

Abstract 5251: Defective Inter-domain Interaction May Cause Spontaneous Ca 2+ Release Via Reduced Affinity of Calmodulin Binding to RyR2 in Failing Hearts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Makoto Ono ◽  
Masafumi Yano ◽  
Takeshi Suetomi ◽  
Xiaojuan Xu ◽  
Hitoshi Uchinoumi ◽  
...  
Keyword(s):  
Domain Interaction ◽  
Mutation Site ◽  
Calmodulin Binding ◽  
Large Size ◽  
Rv Pacing ◽  
Co Addition ◽  
Domain Peptide ◽  
Fluorescence Quencher ◽  
A Site

We previously reported that interaction between N-terminal 1–600 and central domains 2000–2500 of ryanodine receptor (RyR2), harboring many mutation sites in CPVT, is defective (i.e. domain unzipping) in failing hearts. Here, we investigated the pathogenic role of calmodulin (CaM), one of the accessory proteins in RyR2, on Ca 2+ release in failing hearts. Sarcoplasmic reticulum (SR) vesicles were isolated from dog LV muscles {normal (N), n=6; 4-weeks rapid RV pacing (HF: n=6). To assess CaM binding to RyR2, SR was mixed with CaM-SANPAH conjugate (16nM-1μM), followed by UV photolysis. Then, the RyR2-bound CaM was detected by Western blotting using anti-CaM antibody. The affinity of CaM binding to RyR2 was lower in failing SR than normal SR (Kd: 47nM in HF: 19nM in N , p<0.01). To assess the possible relationship between domain unzipping and CaM dissociation from RyR2, RyR2 was also fluorescently labeled with methylcoumarin acetamido (MCA) using DP 2460–2495 (DPc10), which harbors a mutation site in CPVT; R2474S, as a site-directing carrier. In failing SR, domain unzipping was already taken place, as evidenced by an increased accessibility of the bound MCA to a large-size fluorescence quencher. Interestingly, addition of FK506 (10 μM), which was found to dissociate FKBP12.6 from RyR2 and to induce domain unzipping mimicking failing SR, to normal SR indeed reduced the CaM binding affinity to RyR2. In saponin-permeabilized, failing cardiomyocytes ([Ca 2+ ]=buffered at 75 nM), the frequency of Ca 2+ sparks was markedly increased (SpF; s −1 ·100μm −1 : 13.9±0.63 in HF; 7.3±0.6 in N, p<0.01). Addition of CaM (1 μM) in the presence of KN-93 (CaMKII inhibitor) inhibited the increase in SpF (7.9 ±0.41 , p<0.01). This CaM’s effect was, however, markedly inhibited by co-addition of CaM-binding domain peptide within RyR2 (3583–3603) (10.4±0.65, p=ns), strongly suggesting that the re-binding of CaM to RyR2 corrects the abnormal Ca 2+ release in failing cardiomyocytes. In conclusion, the defective inter-domain interaction between N-terminal and central domains within RyR2 seems to increase spontaneous Ca 2+ release events in failing SR, via the reduced CaM-binding to RyR2. Fixing CaM binding to RyR2 may be protective against the diastolic Ca 2+ release in failing hearts.

Crystallographic Studies of PDZ Domain–Peptide Interactions of the Scribble Polarity Module

2021 ◽  
pp. 125-135
Author(s):  
Janesha C. Maddumage ◽  
Bryce Z. Stewart ◽  
Patrick O. Humbert ◽  
Marc Kvansakul
Keyword(s):  
Pdz Domain ◽  
Peptide Interactions ◽  
Domain Peptide

Breast Cancer Multi-classification through Deep Neural Network and Hierarchical Classification Approach

2019 ◽  
Vol 79 (21-22) ◽  
pp. 15481-15511 ◽  
Author(s):  
Ghulam Murtaza ◽  
Liyana Shuib ◽  
Ghulam Mujtaba ◽  
Ghulam Raza
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Deep Neural Network ◽  
Hierarchical Classification ◽  
Classification Approach ◽  
Multi Classification

A Quantitative Fluorescence-Based Assay for Assessing LIM Domain-Peptide Interactions

2016 ◽  
Vol 55 (42) ◽  
pp. 13236-13239 ◽  
Author(s):  
Neil O. Robertson ◽  
Manan Shah ◽  
Jacqueline M. Matthews
Keyword(s):  
Lim Domain ◽  
Peptide Interactions ◽  
Domain Peptide ◽  
Quantitative Fluorescence

scholarly journals Malignant hyperthermia mutation sites in the Leu2442–Pro2477 (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area

2006 ◽  
Vol 401 (1) ◽  
pp. 333-339 ◽  
Author(s):  
Mark L. Bannister ◽  
Tomoyo Hamada ◽  
Takashi Murayama ◽  
Peta J. Harvey ◽  
Marco G. Casarotto ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Structural Studies ◽  
Amino Acid Residues ◽  
Domain Interaction ◽  
Closed State ◽  
Interdomain Interaction ◽  
Ryanodine Receptor 1 ◽  
Domain Peptide ◽  
Interdomain Interactions

To explain the mechanism of pathogenesis of channel disorder in MH (malignant hyperthermia), we have proposed a model in which tight interactions between the N-terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed state of the channel, but mutation in these domains weakens the interdomain interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide corresponding to residues Leu2442–Pro2477 of the central domain, also weakens the domain interaction and produces MH-like channel destabilization, whereas an MH mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve as excellent tools for structure–function studies. Other MH mutations have been reported in the literature involving three other amino acid residues in the DP4 region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the activity of several mutants of DP4 at these three residues. The ability to activate ryanodine binding or to effect Ca2+ release was severely diminished for each of the MH mutants. Other substitutions were less effective. Structural studies, using NMR analysis, revealed that the peptide has two α-helical regions. It is apparent that the MH mutations are clustered at the C-terminal end of the first helix. The data in the present paper indicates that mutation of residues in this region disrupts the interdomain interactions that stabilize the closed state of the channel.

scholarly journals A Multireporter Bacterial 2-Hybrid Assay for the High-Throughput and Dynamic Assay of PDZ Domain–Peptide Interactions

2019 ◽  
Vol 8 (5) ◽  
pp. 918-928 ◽  
Author(s):  
David M. Ichikawa ◽  
Carles Corbi-Verge ◽  
Michael J. Shen ◽  
Jamie Snider ◽  
Victoria Wong ◽  
...  
Keyword(s):  
High Throughput ◽  
Pdz Domain ◽  
Peptide Interactions ◽  
Dynamic Assay ◽  
Domain Peptide

Abstract 944: Tight Binding Of Calmodulin To The Cardiac Ryanodine Receptor May Reduce The Spontaneous Ca 2+ Release Events Induced By Mutation-linked, Defective Inter-domain Interaction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Xiaojuan Xu ◽  
Masafumi Yano ◽  
Makoto Ohno ◽  
Hitoshi Uchinoumi ◽  
Hiroki Tateishi ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Release Kinetics ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Critical Role ◽  
Polymorphic Ventricular Tachycardia ◽  
Fluorescence Labeling ◽  
Domain Interaction ◽  
Human Mutation ◽  
Domain Peptide ◽  
Cardiac Ryanodine Receptor

Interaction between N-terminal 1– 600 and central domains 2000 –2500 of ryanodine receptor (RyR2), where many mutations have been found in patients with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2) or catecholaminergic polymorphic ventricular tachycardia (CPVT), was recently found to play a critical role in channel regulation. Using the domain peptide approach, here, we investigated the role of calmodulin (CaM), one of the accessory proteins of the cardiac ryanodine receptor (RyR2), on Ca 2+ release kinetics. Sarcoplasmic reticulum (SR) vesicles were isolated from dog LV muscles (n=4), then RyR2 was fluorescently labeled with methylcoumarin acetate (MCA) using DP 163–195 , which harbors a human mutation site in ARVC (R176Q), as a site-directing carrier. DP 163–195 mediated a specific MCA fluorescence labeling of central domain (60Kd) of RyR2. Addition of DP 163–195 to the MCA-labeled SR competitively induced the domain unzipping between N-terminal and central domains, as evidenced by an increased accessibility of the bound MCA to a large-size fluorescence quencher. In saponin-permeabilized cardiomyocytes, the addition of DP 163–195 markedly increased the frequency of Ca 2+ sparks (SpF; s −1 ·100μm −1 :13.1±0.9, p<0.01), compared with normal cells (6.9±0.3). Addition of recombinant CaM (100nM), in the presence of KN-93 (CaMKII inhibitor), inhibited the DP 163–195 -induced increase in SpF (7.2±0.5, p<0.01). This effect of CaM was, however, abolished by co-addition of the antibody against the binding site of CaM within RyR2 (3583–3603) (SpF:12.9±0.7, p=ns), strongly suggesting that the binding of CaM to RyR2 corrects the abnormal Ca 2+ release induced by DP 163–195 . The mutation made in the domain peptide, mimicking the same human mutation in ARVC (R176Q) abolished all of the effects that would have been produced by DP 163–195 . In conclusion, the mutation-linked defective inter-domain interaction between N-terminal and central domains within RyR2 (viz. domain unzipping) may increase spontaneous Ca 2+ release, perhaps by weakening CaM-binding to RyR2. Restored binding of CaM to RyR2 may correct defective channel gating of the mutant RyR2.

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