Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca(2+) channel.
Channels 10(1):55 (2016)
The modulation and regulation of voltage-gated Ca(2+) channels is affected by the pore-forming segments, the cytosolic parts of the channel, and interacting intracellular proteins. In this study we demonstrate a direct physical interaction between the N terminus (NT) and C terminus (CT) of the m...
Prosthodontic Considerations in Post-cancer Reconstructions.
Oral and Maxillofacial Surgery Clinics of North... 27(2):255 (2015)
The restoration of function after oncologic surgery of the oral cavity constitutes one of the major challenges facing head and neck oncology. Within the general objective of securing esthetic as well as functional reconstructions, dental rehabilitation is crucial for achieving a good outcome. Ad...
Structural basis of a Kv7.1 potassium channel gating module: studies of the intracellular c-terminal domain in complex with calmodulin.
Structure 22(11):1582 (2014)
Kv7 channels tune neuronal and cardiomyocyte excitability. In addition to the channel membrane domain, they also have a unique intracellular C-terminal (CT) domain, bound constitutively to calmodulin (CaM). This CT domain regulates gating and tetramerization. We investigated the structure of the...
Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂.
Journal of Cell Science 127(Pt 18):3943 (2014)
KCNQ1 and KCNE1 co-assembly generates the I(KS) K(+) current, which is crucial to the cardiac action potential repolarization. Mutations in their corresponding genes cause long QT syndrome (LQT) and atrial fibrillation. The A-kinase anchor protein, yotiao (also known as AKAP9), brings the I(KS) ...
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development.
Nucleic Acids Research 42(15):9761 (2014)
The COP9 signalosome protein complex has a central role in the regulation of development of multicellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may functio...
APP homodimers transduce an amyloid-β-mediated increase in release probability at excitatory synapses.
Cell Reports 7(5):1560 (2014)
Accumulation of amyloid-β peptides (Aβ), the proteolytic products of the amyloid precursor protein (APP), induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer's disease. While depression of synaptic transmiss...
Ancient origins of RGK protein function: modulation of voltage-gated calcium channels preceded the protostome and deuterostome split.
PLoS ONE 9(7):e100694 (2014)
RGK proteins, Gem, Rad, Rem1, and Rem2, are members of the Ras superfamily of small GTP-binding proteins that interact with Ca2+ channel β subunits to modify voltage-gated Ca2+ channel function. In addition, RGK proteins affect several cellular processes such as cytoskeletal rearrangement, neuro...
Population shift underlies Ca2+-induced regulatory transitions in the sodium-calcium exchanger (NCX).
Journal of Biological Chemistry 288(32):23141 (2013)
In eukaryotic Na(+)/Ca(2+) exchangers (NCX) the Ca(2+) binding CBD1 and CBD2 domains form a two-domain regulatory tandem (CBD12). An allosteric Ca(2+) sensor (Ca3-Ca4 sites) is located on CBD1, whereas CBD2 contains a splice-variant segment. Recently, a Ca(2+)-driven interdomain switch has been ...
Structural flexibility of CaV1.2 and CaV2.2 I-II proximal linker fragments in solution.
Biophysical Journal 104(11):2392 (2013)
Voltage-dependent calcium channels (CaV) enable the inward flow of calcium currents for a wide range of cells. CaV1 and CaV2 subtype α1 subunits form the conducting pore using four repeated membrane domains connected by intracellular linkers. The domain I-II linker connects to the membrane gate ...
Competitive and non-competitive regulation of calcium-dependent inactivation in CaV1.2 L-type Ca2+ channels by calmodulin and Ca2+-binding protein 1.
Journal of Biological Chemistry 288(18):12680 (2013)
CaV1.2 interacts with the Ca(2+) sensor proteins, calmodulin (CaM) and calcium-binding protein 1 (CaBP1), via multiple, partially overlapping sites in the main subunit of CaV1.2, α1C. Ca(2+)/CaM mediates a negative feedback regulation of Cav1.2 by incoming Ca(2+) ions (Ca(2+)-dependent inactivat...
The organization of a CSN5-containing subcomplex of the COP9 signalosome.
Journal of Biological Chemistry 287(50):42031 (2012)
The COP9 signalosome (CSN) is an evolutionarily conserved multi-protein complex that interfaces with the ubiquitin-proteasome pathway and plays critical developmental roles in both animals and plants. Although some subunits are present only in an ∼320-kDa complex-dependent form, other subunits a...
The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.
Journal of Neuroscience 32(22):7602 (2012)
Voltage-dependent calcium channels (VDCCs) allow the passage of Ca(2+) ions through cellular membranes in response to membrane depolarization. The channel pore-forming subunit, α1, and a regulatory subunit (Ca(V)β) form a high affinity complex where Ca(V)β binds to a α1 interacting domain in the...
A common Ca2+-driven interdomain module governs eukaryotic NCX regulation.
PLoS ONE 7(6):e39985 (2012)
Na(+)/Ca(2+) exchanger (NCX) proteins mediate Ca(2+)-fluxes across the cell membrane to maintain Ca(2+) homeostasis in many cell types. Eukaryotic NCX contains Ca(2+)-binding regulatory domains, CBD1 and CBD2. Ca(2+) binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, w...
Ca(V)1.2 I-II linker structure and Timothy syndrome.
Channels 6(6):468 (2012)
Ca(V) channels are multi-subunit protein complexes that enable inward cellular Ca(2+) currents in response to membrane depolarization. We recently described structure-function studies of the intracellular α1 subunit domain I-II linker, directly downstream of domain IS6. The results show the exte...
RGK family G-domain:GTP analog complex structures and nucleotide-binding properties.
Journal of Molecular Biology 413(2):372 (2011)
The RGK family of small G-proteins, including Rad, Gem, Rem1, and Rem2, is inducibly expressed in various mammalian tissues and interacts with voltage-dependent calcium channels and Rho kinase. Many questions remain regarding their physiological roles and molecular mechanism. Previous crystallog...
Regulation of neuronal M-channel gating in an isoform-specific manner: functional interplay between calmodulin and syntaxin 1A.
Journal of Neuroscience 31(40):14158 (2011)
Whereas neuronal M-type K(+) channels composed of KCNQ2 and KCNQ3 subunits regulate firing properties of neurons, presynaptic KCNQ2 subunits were demonstrated to regulate neurotransmitter release by directly influencing presynaptic function. Two interaction partners of M-channels, syntaxin 1A an...
COP9 signalosome subunit 7 from Arabidopsis interacts with and regulates the small subunit of ribonucleotide reductase (RNR2).
Plant Molecular Biology 77(1-2):77 (2011)
The COP9 Signalosome protein complex (CSN) is a pleiotropic regulator of plant development and contains eight-subunits. Six of these subunits contain the PCI motif which mediates specific protein interactions necessary for the integrity of the complex. COP9 complex subunit 7 (CSN7) contains an N...
Beclin 1 self-association is independent of autophagy induction by amino acid deprivation and rapamycin treatment.
Journal of Cellular Biochemistry 110(5):1262 (2010)
Autophagy, a process of self-digestion of cellular constituents, regulates the balance between protein synthesis and protein degradation. Beclin 1 represents an important component of the autophagic machinery. It interacts with proteins that positively regulate autophagy, such as Vps34, UVRAG, a...
An S-acylation switch of conserved G domain cysteines is required for polarity signaling by ROP GTPases.
Current Biology 20(10):914 (2010)
Rho GTPases are master regulators of cell polarity. For their function, Rhos must associate with discrete plasma membrane domains. Rho of Plants (ROPs) or RACs comprise a single family. Prenylation and S-acylation of hypervariable domain cysteines of Ras and Rho GTPases are required for their fu...
Intracellular domains interactions and gated motions of I(KS) potassium channel subunits.
EMBO Journal 28(14):1994 (2009)
Voltage-gated K(+) channels co-assemble with auxiliary beta subunits to form macromolecular complexes. In heart, assembly of Kv7.1 pore-forming subunits with KCNE1 beta subunits generates the repolarizing K(+) current I(KS). However, the detailed nature of their interface remains unknown. Mutati...