As long as most healthy cells do not have the docking site for that T cell protein, the treatment can work.
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Situated in front of the gene, this switch, called an enhancer, is a docking site for proteins that control the gene's activity.
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Dr. Aghajanian and Dr. Epstein began by placing a docking site on scar tissue cells in the hearts of mice with heart failure.
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It is like having the precise dimensions of the International Space Station so that you can design a spacecraft that can fits perfectly in the docking site.
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It acts as a docking site for complex-mediated phosphorylation. The gene is located within the Smith-Magenis syndrome region on chromosome 17.
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A large coiled-coil protein, C-Nap1, is a docking site for the fibrous tether to proximal ends of centrioles which Rootletin physically interacts with. Furthermore, Rootletin is phosphorylated by Nek2 kinase.
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Small molecule allosteric activators of PDPK1 were shown to selectively inhibit activation of substrates that require docking site interaction. These compounds do not bind to the active site and allow PDPK1 to activate other substrates that do not require docking site interaction. PDPK1 is constitutively active and at present, there is no known inhibitor proteins for PDPK1. The activation of PDPK1's main effector, AKT, is believed to require a proper orientation of the kinase and PH domains of PDPK1 and AKT at the membrane.
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The structure of PDPK1 can be divided into two domains; the kinase or catalytic domain and the PH domain. The PH domain functions mainly in the interaction of PDPK1 with phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate which is important in localization and activation of some of membrane associated PDPK1's substrates including AKT. The kinase domain has three ligand binding sites; the substrate binding site, the ATP binding site, and the docking site (also known as PIF pocket). Several PDPK1 substrates including S6K and Protein kinase C, require the binding at this docking site.
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The park has two developed areas: Windigo, at the southwest end of the island (docking site for the ferries from Minnesota), with a campstore, showers, campsites, rustic camper cabins for those wanting to sleep off of the ground and a boat dock. Rock Harbor on the south side of the northeast end (docking site for the ferries from Michigan), with a campstore, showers, restaurant, lodge, campsites, and a boat dock. Non-camping sleeping accommodations at the park are limited to the lodge at Rock Harbor and the camper cabins at Windigo.
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EMBO Rep. 3, 341–348 (2002). PBD has high affinity for proteins already phosphorylated at certain serine/threonine sites. This requires priming of substrates by Plk itself or other kinases such as Cdk1 to create a docking site.
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Ku is a basket-shaped molecule that slides onto the DNA end and translocates inward. Ku may function as a docking site for other NHEJ proteins, and is known to interact with the DNA ligase IV complex and XLF.
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R-SMAD binds coSMAD The phosphorylated RSMAD has a high affinity for a coSMAD (e.g. SMAD4) and forms a complex with one. The phosphate group does not act as a docking site for coSMAD, rather the phosphorylation opens up an amino acid stretch allowing interaction.
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Dimerization brings the two receptors into close proximity. This stimulates the kinase activity of EGFR, which leads to transautophosphorylation on multiple tyrosine residues in C-terminal end of the molecule. The phosphorylated tyrosine residue can then serve as a docking site for downstream signaling proteins. (Fig. 1).
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In addition, the first 8 residues of the CXCL12 N-terminal serve as a receptor binding site, though only Lys-1 and Pro-2 directly participated in activating the receptor. Meanwhile, the RFFESH motif (residues 12-17) in the loop region function as a docking site for CXCL12 receptor binding.
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The newly found molecule had the added advantage of enhancing 4E-BP1 binding, a surprise given that this molecule is also believed to bind eIF4E via the same motif. It appears that by displacing the eIF4G sequence without blocking the entire binding interface of eIF4E, 4EGI-1 is able to clear the “docking site” of the endogenous regulator.
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Clb5 processivity is dependent on the T5 and T33 sites, while Cln2 processivity is dependent on T5. Reintroduction of various residues led to the discovery of the T33 residue serving as a docking site for the T45/T48 phosphodegron pair, which is able to promote Sic1 degradation to a certain extent in the absence of other phosphodegron pairs.
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The ATP binding domain consists of four subdomains split into two lobes by a central ATP/ADP binding pocket. The two terminal domains are linked together by a conserved region referred to as loop LL,1, which is critical for allosteric regulation. The unstructured region at the very end of the C-terminal is believed to be the docking site for co- chaperones.
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These American officers informed Australia about the location of Tukuran as a good docking site. In the morning of January 25, 1945 at about 11:00 a US sea plane "Santa Catalina" landed on the beach to unload supplies. During liberation period, American planes in V-formation fly in the sky. Displaced Tukuranons returned home and started to fix their abandoned homes.
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Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.
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The ATP binding domain consists of four subdomains split into two lobes by a central ATP/ADP binding pocket. The two terminal domains are linked together by a conserved region referred to as loop LL,1, which is critical for allosteric regulation. The unstructured region at the very end of the C-terminal is believed to be the docking site for co- chaperones.
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CD33 can be stimulated by any molecule with sialic acid residues such as glycoproteins or glycolipids. Upon binding, the immunoreceptor tyrosine-based inhibition motif (ITIM) of CD33, present on the cytosolic portion of the protein, is phosphorylated and acts as a docking site for Src homology 2 (SH2) domain-containing proteins like SHP phosphatases. This results in a cascade that inhibits phagocytosis in the cell.
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PIP3 is a membrane-docking site for AKT and PDK1. In turn, active PDK1, along with mTORC1, phosphorylates S6K in the part of the mTOR pathway which promotes protein synthesis and cell growth. The mTOR pathway has also been found to be involved in aging. Studies with C. elegans, fruitflies, and mice have shown that the lifespan of the organism is significantly increased by inhibiting mTORC1.
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MET signaling complex MET activation by its ligand HGF induces MET kinase catalytic activity, which triggers transphosphorylation of the tyrosines Tyr 1234 and Tyr 1235. These two tyrosines engage various signal transducers, thus initiating a whole spectrum of biological activities driven by MET, collectively known as the invasive growth program. The transducers interact with the intracellular multisubstrate docking site of MET either directly, such as GRB2, SHC, SRC, and the p85 regulatory subunit of phosphatidylinositol-3 kinase (PI3K), or indirectly through the scaffolding protein Gab1 Tyr 1349 and Tyr 1356 of the multisubstrate docking site are both involved in the interaction with GAB1, SRC, and SHC, while only Tyr 1356 is involved in the recruitment of GRB2, phospholipase C γ (PLC-γ), p85, and SHP2. GAB1 is a key coordinator of the cellular responses to MET and binds the MET intracellular region with high avidity, but low affinity.
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T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells and B cells) via the MHC. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase Lck. Lck phosphorylates the intracellular portions of the CD3 complex (called ITAMs), creating a docking site for ZAP-70.
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L23 protein functions as a chaperone docking site on the ribosome. and targeting.Ataide SF, Schmitz N, Shen K, Ke A, Shan SO, Doudna JA, Ban N. (2011) The Crystal Structure of the Signal Recognition Particle in Complex with Its Receptor. Science 331(6019):881-886Estrozi LF, Boehringer D, Shan SO, Ban N, Schaffitzel C. (2010) Cryo-EM structure of the E. coli translating ribosome in complex with SRP and its receptor.
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The essential region for inactivation in sodium channels is four amino acid sequence made up of isoleucine, phenylalanine, methionine and threonine (IFMT). The T and F interact directly with the docking site in the channel pore. When voltage-gated sodium channels open, the S4 segment moves outwards from the channel and into the extracellular side. This exposes hydrophobic residues in the S4 and S5 segments which interact with the inactivation ball.
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Kalayaan municipal officials have proposed that this island be populated with civilian settlers "within the coming years". If accomplished, it will be the second barangay of Kalayaan (after Thitu Island/Pag-asa). However, only naval vessels are currently capable of reaching the island. An estimate of 300 million pesos (US$7.5M) will be needed to construct an airstrip, a docking site, some land reclamation and other structures necessary to support an isolated community.
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The port is closely connected by land to the city's airport. This port is the docking site for small private vessels and yachts owned by David's residents, and also serves as an attraction for fishers. It is also the departing place for tours that go to the numerous islands of the Chiriquí Gulf and the base of operations of many handicraft vendors. The city is the seat of the Roman Catholic Diocese of David.
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The LAMTOR 1 dimer does not have the same structure as the other subunits. LAMTOR 1 surrounds most of the two heterodimers, providing structural support and keeping the heterodimers in place. When amino acids are present, the subunits are folded and positioned in such a way that allows for the Rag-GTPases to be anchored to its primary docking site of LAMTOR 2/3 on the Ragulator. The Rag-GTPases consist of two sets of heterodimers; RAGs A/B and RAGs C/D.
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Additionally, the N-terminus has an alpha helical segment that is held to the inside wall of the pore by hydrophobic interactions with residues on β-sheets 8-18. This N-terminus can serve as a scaffold for the movement of ions or attachment of proteins. One such example is seen as it is the docking site for HK1 binding. A significant residue to point out is the glutamate located at the 73rd residue on the amino acid chain (E73).
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Second, MAPK primes Smad4 for GSK3-mediated phosphorylations that cause transcriptional inhibition and also generate a phosphodegron used as a docking site by the ubiquitin E3 ligase Beta-transducin Repeat Containing (beta-TrCP) that polyubiquitinates Smad4 and targets it for degradation in the proteasome. Smad4 GSK3 phosphorylations have been proposed to regulate the protein stability during pancreatic and colon cancer progression. In the nucleus the heteromeric complex binds promoters and interact with transcriptional activators. SMAD3/SMAD4 complexes can directly bind the SBE.
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SBDβ contains the peptide binding pocket while SBDα serves as a lid to cover the substrate binding cleft. The ATP binding domain consists of four subdomains split into two lobes by a central ATP/ADP binding pocket. The two terminal domains are linked together by a conserved region referred to as loop LL,1, which is critical for allosteric regulation. The unstructured region at the very end of the C-terminal is believed to be the docking site for co-chaperones.
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This processivity is also dependent on the presence of the cyclin docking site since increasing the numbers of mutations in this site decreases the net phosphorylation rate. Processive phosphorylation has two plausible mechanisms where a single binding event leads to the phosphorylation of two or more sites. The first mechanism proposes that, without dissociating from the enzyme complex, the primary site is phosphorylated and immediately shifted from the active site to the Cks1 binding pocket to allow for the additional phosphorylation of other CDK sites.
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A 2014 study noted that AMPK (AMP-activated protein kinase) and mTOR play important roles in managing different metabolic programs. It was also found that the protein complex v-ATPase-Ragulator was essential for activation of mTOR and AMPK. The v-ATPase-Ragulator complex is also used as an initiating sensor for energy stress, and serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex. This allows a switch between catabolism and anabolism.
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The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signalling proteins bind including SLP-76. SLP-76 is also phosphorylated by ZAP-70, which requires its activation by Src family kinases.
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However, several structural details set ALDOC apart. For instance, the Arg303 residue in ALDOC adopts an intermediate conformation between the liganded and unliganded structures observed in the other isozymes. Also, the C-terminal region between Glu332 and Lys71 forms a salt bridge with the barrel region that is absent in the A and B isoforms. Moreover, the electrostatic surface of ALDOC is more negatively charged, which may serve as an acidic binding site or as a docking site to accommodate the C-terminal conformations.
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Both p90 and p70 Rsk phosphorylate ribosomal protein s6, part of the translational machinery, but several other substrates have been identified, including other ribosomal proteins. Cytosolic substrates of p90rsk include protein phosphatase 1; glycogen synthase kinase 3 (GSK3); L1 CAM, a neural cell adhesion molecule; Son of Sevenless, the Ras exchange factor; and Myt1, an inhibitor of cdc2. RSK phosphorylation of SOS1 (Son of Sevenless) at Serines 1134 and 1161 creates 14-3-3 docking site. This interaction of phospho SOS1 and 14-3-3 negatively regulates Ras-MAPK pathway.
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Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin- homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s).
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Signal-mediated nuclear import and export proceed through the nuclear pore complex (NPC), which is composed of approximately 30 unique proteins collectively known as nucleoporins. The 98 kD nucleoporin is generated through a biogenesis pathway that involves synthesis and proteolytic cleavage of a 186 kD precursor protein. This cleavage results in the 98 kD nucleoporin as well as a 96 kD nucleoporin, both of which are localized to the nucleoplasmic side of the NPC. Rat studies show that the 98 kD nucleoporin functions as one of several docking site nucleoporins of transport substrates.
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D-motifs essentially consist of one or two positively charged amino acids, followed by alternating hydrophobic residues (mostly leucines), typically upstream of the phosphorylation site by 10–50 amino acids. Many of the known MAPK substrates contain such D-motifs that can not only bind to, but also provide specific recognition by certain MAPKs. D-motifs are not restricted to substrates: MAP2 kinases also contain such motifs on their N-termini that are absolutely required for MAP2K-MAPK interaction and MAPK activation. Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the same docking site.
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LC3 shares structural homology with ubiquitin, and therefore has been termed a ubiquitin-like protein. LC3 has a LDS (LIR docking site)/hydrophobic binding interface in the N terminus which interacts with LIR (LC3 Interacting Region) containing proteins. This domain is rich in hydrophobic amino acids, the mutation of which impairs the ability of LC3 binding with LIR containing proteins, many of which are autophagy cargo adapter proteins. For example, sequestosome (SQSTM1) interacts with Phe 52 and Leu53 aminoacids present in hydrophobic binding interface of LC3 and any mutation of these amino acids prevents LC3 interaction with SQSTM1.
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The general dRMCE strategy takes advantage of the fact that most conditional alleles encode a selection cassette flanked by FRT sites, in addition to loxP sites that flank functionally relevant exons ('floxed' exons). The FRT-flanked selection cassette is in general placed outside the loxP-flanked region, which renders these alleles directly compatible with dRMCE. Simultaneous expression of Cre and Flp recombinases induces cis recombination and formation of the deleted allele, which then serves as a 'docking site' at which to insert the replacement vector by trans recombination. The correctly replaced locus would encode the custom modification and a different drug-selection cassette flanked by single loxP and FRT sites.
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The Upper Newport Bay is one of the last remaining natural estuaries in Southern California; that is, it is a very lush area of land that is home to fish, birds, and other animals. This land is important to migrating birds; it is used as just rest stop or a permanent winter dwelling for birds coming from Alaska or Canada and the spring it is a habitat for birds from the south. The upper bay serves as a barrier for industry of the lower bay and beaches in Newport. The beaches serve as playing group for families and the harbor serves as a docking site for boats.
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Mice with truncated EpoR are viable, which suggests Jak2 activity is sufficient to support basal erythropoiesis by activating the necessary pathways without phosphotyrosine docking sites being needed. EpoR-H form of EpoR truncation contains the first, and, what can be argued, the most important tyrosine 343 that serves as a docking site for the Stat5 molecule, but lacks the rest of the cytoplasmic tail. These mice exhibit elevated erythropoiesis consistent with the idea that phosphatase recruitment (and therefore the shutting down of signaling) is aberrant in these mice. The EpoR-HM receptor also lacks the majority of the cytoplasmic domain, and contains the tyrosine 343 that was mutated to phenylalanine, making it unsuitable for efficient Stat5 docking and activation.
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The park is a joint project of Department of Tourism Region V and the Local Government Unit of Camaligan, Camarines Sur under the Bottom- Up Budgeting Program for the year 2015. In 2014, it was planned only to be the docking site of the Camaligan River Cruise or M/B Camaligan, thus, first naming the park as Camaligan River Cruise Park. Being located near the Bicol River, the people of Camaligan gained their socio-cultural identity as river people and traders during pre-colonialism. The idea of building the park was to promote the town's culture and bring life to the river as it is a reminder of Camaligan's significant contribution in the history and its integral role for the emergence of Bicol civilization.
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Once the focal point of downtown Houston, a small historical park was dedicated at the site in 1967. The Southern Pacific Railroad donated of land to the park project, which was to be developed and maintained by the Houston Chamber of Commerce, the City of Houston, and the Harris County Navigation District. In addition, a marker was placed at the park to indicate where, in 1837, townspeople erected a liberty pole to commemorate Sam Houston's victory over Santa Anna at the Battle of San Jacinto the previous year. For a brief period in the 1990s, Allen's Landing was once again the docking site for the Laura, a sightseeing boat that was a namesake of the 19th century vessel. The name Allen’s Landing is a 20th- century creation not found in any historical document.
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Evidence from yeast two-hybrid analysis, coimmunoprecipitation from in vitro synthesis, and coimmunoprecipitation from cell extracts shows that the site of interaction is between the terminal amino group of FANCA and the central part of BRCA1, located within amino acids 740–1083. However, as FANCA and BRCA1 undergo a constitutive interaction, this may not depend solely on detection of actual DNA damage. Instead BRCA1 protein may be more crucial in the detection of double stranded DNA breaks, or an intermediate in interstrand crosslink (ICL) repair, and rather serve to bring some of the many DNA repair proteins it interacts with to the site. One such protein would be FANCA, which in turn may serve as a docking site or anchor point at the site of ICL damage for the FA core complex.
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Once at Earth-Moon L2, Skylab II could be a "stepping stone" for further human exploration in the Solar System, for example by being a docking site for a crewed lunar lander before the trip to the Moon. The second use would be to add a servicing capability for the astrophysics missions located near Earth-Sun L2, extending the cryogenic mission lifetime of such missions by continually refilling their liquid helium and enabling some astrophysics missions which may otherwise have not been possible or would have been launched in a less-capable state. For extravehicular activities (EVAs) near the space station, a small, one-person FlexCraft may be used in lieu of a spacesuit to improve dexterity and safety for astronauts, as well as the efficiency of EVAs. FlexCraft would eliminate the requirement of an astronaut to prebreathe the pure oxygen atmosphere in a spacesuit, reducing overhead time for EVAs significantly and enabling longer EVAs to be carried out.
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