Structural Diversity in Calmodulin - Peptide Interactions

Dürvanger, Zsolt; Harmat, V.

doi:10.2174/1389203720666190925101937

Cited by 10 publications

(9 citation statements)

References 75 publications

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“…The structural constraints for a CaM-binding motif are not so strict, 8 thus target orientation, distances of their anchoring residues and orientation of the CaM lobes can vary within the CaM-target complexes (reviewed in Ref. [10][11][12]). Nevertheless, several proteins can bind to CaM at low Ca 2+ concentrations or independently of calcium (IQ motifs).…”

Section: Introductionmentioning

confidence: 99%

Comparison of ligand binding and conformational stability of human calmodulin with its homolog from the malaria parasitePlasmodium falciparum

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Comparison of ligand binding and conformational stability of human calmodulin with its homolog from the malaria parasitePlasmodium falciparum

et al. 2020

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“…Canonical motifs for Ca 2 -dependent binding of CaM usually consist of an α-helix with two bulky, hydrophobic amino acids (W, F, I, L, V) at the first and last positions, spaced by a short stretch of a variable number of residues [ 25 ]. The motifs involved in Ca 2+ -dependent binding of CaM are classified according to the position of the hydrophobic amino acids involved in the binding [ 25 , 26 ]. Our mutational and structural analyses indicated that the CaMBS of INF2 corresponds to a 1-4-8 motif in which W11 occupies the position 1 and L14 and L18 the positions 4 and 8, respectively.…”

Section: Resultsmentioning

confidence: 99%

Structure and function of the N-terminal extension of the formin INF2

Labat-de-Hoz

Comas

Rubio-Ramos

et al. 2022

Cell. Mol. Life Sci.

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In INF2—a formin linked to inherited renal and neurological disease in humans—the DID is preceded by a short N-terminal extension of unknown structure and function. INF2 activation is achieved by Ca2+-dependent association of calmodulin (CaM). Here, we show that the N-terminal extension of INF2 is organized into two α-helices, the first of which is necessary to maintain the perinuclear F-actin ring and normal cytosolic F-actin content. Biochemical assays indicated that this helix interacts directly with CaM and contains the sole CaM-binding site (CaMBS) detected in INF2. The residues W11, L14 and L18 of INF2, arranged as a 1-4-8 motif, were identified as the most important residues for the binding, W11 being the most critical of the three. This motif is conserved in vertebrate INF2 and in the human population. NMR and biochemical analyses revealed that CaM interacts directly through its C-terminal lobe with the INF2 CaMBS. Unlike control cells, INF2 KO cells lacked the perinuclear F-actin ring, had little cytosolic F-actin content, did not respond to increased Ca2+ concentrations by making more F-actin, and maintained the transcriptional cofactor MRTF predominantly in the cytoplasm. Whereas expression of intact INF2 restored all these defects, INF2 with inactivated CaMBS did not. Our study reveals the structure of the N-terminal extension, its interaction with Ca2+/CaM, and its function in INF2 activation.

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“…20 Calmodulin (CaM), a Ca 2+ sensor protein, plays an important role in signal transduction pathways by binding with Ca 2+ . 26 CaMKII is activated by the binding of Ca 2+ saturated CaM (Ca 2+ /CaM) in an auto-phosphorylation manner. 27 It is reported that CaMKII is a multi-subunit holoenzyme, which contains a kinase domain, an autoinhibitory/ regulatory domain, an actin binding domain and an association domain.…”

Section: Discussionmentioning

confidence: 99%

UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through TRPA1 Channels

Liu¹,

Li²,

Wu³

et al. 2022

CCID

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Ultraviolet radiation (UVR) enhances skin pigmentation, which involves the production of melanin by melanocytes and subsequent transfer to keratinocytes. In the epidermis, keratinocyte phagocytosis plays a pivotal role in the process of melanosome transfer to protect DNA of epidermal cells against damage from UVR. Previous research suggested that transient receptor potential channels ankyrin 1 (TRPA1) was required for UVR-induced early melanin synthesis in melanocytes. Currently, there is no evidence that supports the detailed mechanism of TRPA1 for UVR-induced phagocytosis by keratinocytes. Here, we investigated the effect and the possible mechanisms of TRPA1 on keratinocyte phagocytosis and skin pigmentation after UVR exposure. Methods: Flow cytometry was applied to investigate the effect of TRPA1 on intracellular calcium concentration ([Ca 2+ ] ic ) and fluorescent microspheres uptake was carried out to analyze phagocytosis in HaCaT cells (human immortalized keratinocytes). Western blotting was applied to measure the protein expression of calcium/calmodulin-dependent protein kinase II (CaMKII), phosphorylated CaMKII and β-catenin after UVA/UVB exposure. Masson-Fontana staining was applied to observe the effect of XAV-939 (decreasing the expression of β-catenin) on UVB-induced skin pigmentation in guinea pigs. Results: TRPA1 channels activated by UVR increased the [ca 2+ ] ic and phosphorylation of CaMKII in HaCaT cells. The UVR-induced phagocytosis was regulated by TRPA1 in HaCaT cells. TRPA1 promoted the protein expression of β-catenin after UVR exposure in HaCaT cells. XAV-939, inhibiting β-catenin expression, decreased the UVB-induced skin pigmentation on in vivo guinea pig models. Conclusion: Taken together, TRPA1 activated by UVR led to the increase of intracellular calcium, which promoted the phosphorylation of CaMKII, enhancing keratinocyte phagocytosis. Moreover, TRPA1 regulated the protein expression of β-catenin to exert a lightening effect on skin pigmentation. Our findings suggest that TRPA1 may be a potential therapeutic target for UVR-induced skin pigmentary diseases.

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Structural Diversity in Calmodulin - Peptide Interactions

Cited by 10 publications

References 75 publications

Comparison of ligand binding and conformational stability of human calmodulin with its homolog from the malaria parasitePlasmodium falciparum

Comparison of ligand binding and conformational stability of human calmodulin with its homolog from the malaria parasitePlasmodium falciparum

Structure and function of the N-terminal extension of the formin INF2

UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through TRPA1 Channels

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