2010
DOI: 10.1021/bi100500m
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Intrinsically Disordered PEP-19 Confers Unique Dynamic Properties to Apo and Calcium Calmodulin

Abstract: PEP-19 (Purkinje cell protein 4) is an intrinsically disordered protein with an IQ calmodulin (CaM) binding motif. Expression of PEP-19 was recently shown to protect cells from apoptosis and cell death due to Ca 2+ overload. Our initial studies showed that PEP-19 causes novel and dramatic increases in the rates of Ca 2+ association and dissociation from the C-domain of CaM. The goal of this work was to study interactions between C-domain of CaM (C-CaM) and PEP-19 by solution NMR to identify mechanisms by which… Show more

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Cited by 15 publications
(20 citation statements)
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“…Therefore, CaM⅐Orai1-CMBD displays a unique binding mode of CaM to its target peptides, and again shows the flexibility of CaM to bind a large variety of target proteins. In addition to Orai1-CMBD and GAD-CMBD, IQ calmodulin binding peptides from Na V 1.5 (31), Na V 1.2 (32), and PEP-19 (33)(34)(35) bind selectively to the C-lobe of CaM, leaving the N-lobe unoccupied, and thus fall in this group 1-0.…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, CaM⅐Orai1-CMBD displays a unique binding mode of CaM to its target peptides, and again shows the flexibility of CaM to bind a large variety of target proteins. In addition to Orai1-CMBD and GAD-CMBD, IQ calmodulin binding peptides from Na V 1.5 (31), Na V 1.2 (32), and PEP-19 (33)(34)(35) bind selectively to the C-lobe of CaM, leaving the N-lobe unoccupied, and thus fall in this group 1-0.…”
Section: Discussionmentioning
confidence: 99%
“…In this case unconstrained tumbling of the tethered N-domain could propagate an increase in dynamics in the C-lobe. Increased CaM dynamics have previously been associated with rapid dissociation of Ca 2ϩ (33,(57)(58)(59). Alternatively the N-lobe of CaM may make contacts with Ng.…”
Section: Nmr Studies Show That Ng Interacts With Both the N-lobe And mentioning
confidence: 99%
“…This leads to the hypothesis that Ng and PEP-19 may serve analogous roles in the postsynaptic cell but that they might possess unique properties (like crosstalk with the PKC pathway) that permits cell type-specific tuning of their impact on the Ca 2ϩ /CaM signaling pathway. We focus in this report on a quantitative understanding of the biochemical properties of Ng and its interactions with CaM, and we contrast these findings with published information on the related protein PEP-19 (14,33). Ng (ϳ7.8 kDa) and PEP-19 (ϳ6.8 kDa) are small intrinsically disordered proteins that both contain an IQ motif (34,35) preceded by an acidic region composed largely of Asp or Glu residues.…”
mentioning
confidence: 99%
“…Wild-type mammalian calmodulin (CaM) (31)(32)(33), T34C/T110C CaM (17), K75C CaM (34), D2C CaM (35,36), and 15 N-isotope-labeled CaM (31,37,38) were expressed and purified as previously described in the cited works. The target peptide representing the CaM recognition motif for CaMKI (AKSKWKQAFNATAVVRHMRKLQ) was purchased from LifeTein (Somerset, NJ).…”
Section: Protein and Peptide Preparationmentioning
confidence: 99%