Sodium-coupled neurotransmitter transport: structure, function and regulation.

1994 ◽  
Vol 196 (1) ◽  
pp. 237-249 ◽  
Author(s):  
B I Kanner
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Glial Cells ◽  
Plasma Membranes ◽  
Nerve Terminals ◽  
Amino Group ◽  
Amino Acid Residues ◽  
Transmembrane Helices ◽  
Neurotransmitter Transport ◽  
Sodium And Potassium

The removal of neurotransmitters by their transporters--located in the plasma membranes of nerve terminals and glial cells--plays an important role in the termination of synaptic transmission. In the last 3 years, many neurotransmitter transporters have been cloned. Structurally and functionally they can be divided into two groups: glutamate transporters, of which to date three have been cloned, couple the flow of glutamate to that of sodium and potassium. The second group of transporters includes those for GABA, glycine, taurine, norepinephrine, dopamine and serotonin. They are sodium- and chloride-dependent, but do not require potassium for function. One of these, the GABAA transporter, encoded by GAT-1, is perhaps the best characterized. It has been purified and reconstituted and has a molecular mass of around 80 kDa, of which 10-15 kDa is sugar. Amino and carboxyl termini (around 50 amino acids each) are not required for function. The transporter is protected against proteolysis at multiple sites by GABA, provided that the two cosubstrates--sodium and chloride--are present. Several amino acid residues that are critical for function have been identified in the GABA transporter. These include arginine-69 and tryptophan-222 located in the first and fourth putative transmembrane helices, respectively. The first is possibly involved in the binding of chloride. The tryptophan appears to serve as a binding site for the amino group of GABA.

The C-terminal sequence of amino acid residues of κ-casein isolated from buffalo's milk

1967 ◽  
Vol 34 (1) ◽  
pp. 85-88 ◽  
Author(s):  
M. H. Abd El-Salam ◽  
W. Manson
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Peptide Chain ◽  
Amino Acid Residues ◽  
Terminal Sequence ◽  
Carboxypeptidase A ◽  
Phosphorous Content ◽  
Single Peptide

SummaryWhen κ-casein from buffalo's milk was treated with carboxypeptidase A (EC 3. 4. 2. 1),4 amino acids, valine, threonine, serine and alanine were released from the protein in a manner consistent with the view that they originate in the C-terminal sequence of a single peptide chain. The amounts produced suggest a minimum molecular weight for buffalo κ-casein of approximately 17000, in agreement with the value calculated from the phosphorous content on the basis of the presence of 2 phosphorus atoms/molecule. A comparison is made with the C-terminal sequence reported for bovine κ-casein.

Structural characterization of folded and extended conformations in peptides containing γ amino acids with proteinogenic side chains: crystal structures of γn, (αγ)n and γγδγ sequences

2015 ◽  
Vol 39 (5) ◽  
pp. 3319-3326 ◽  
Author(s):  
Madhusudana M. B. Reddy ◽  
K. Basuroy ◽  
S. Chandrappa ◽  
B. Dinesh ◽  
B. Vasantha ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Crystal Structures ◽  
Structural Characterization ◽  
Side Chains ◽  
Amino Acid Residues

γn amino acid residues can be incorporated into structures in γn and hybrid sequences containing folded and extended α and δ residues.

scholarly journals Volta Phase Plate Cryo-EM Structure of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2

2019 ◽  
Vol 20 (4) ◽  
pp. 931 ◽  
Author(s):  
Jean-Marc Jeckelmann ◽  
Dimitrios Fotiadis
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Drug Targets ◽  
Plasma Membranes ◽  
Protein Complexes ◽  
Methylotrophic Yeast ◽  
Disulfide Bridge ◽  
Phase Plate ◽  
Amino Acid Transporters ◽  
Loss Of Function

Heteromeric amino acid transporters (HATs) are protein complexes that catalyze the transport of amino acids across plasma membranes. HATs are composed of two subunits, a heavy and a light subunit, which belong to the solute carrier (SLC) families SLC3 and SLC7. The two subunits are linked by a conserved disulfide bridge. Several human diseases are associated with loss of function or overexpression of specific HATs making them drug targets. The human HAT 4F2hc-LAT2 (SLC3A2-SLC7A8) is specific for the transport of large neutral L-amino acids and specific amino acid-related compounds. Human 4F2hc-LAT2 can be functionally overexpressed in the methylotrophic yeast Pichia pastoris and pure recombinant protein purified. Here we present the first cryo-electron microscopy (cryo-EM) 3D-map of a HAT, i.e., of the human 4F2hc-LAT2 complex. The structure could be determined at ~13 Å resolution using direct electron detector and Volta phase plate technologies. The 3D-map displays two prominent densities of different sizes. The available X-ray structure of the 4F2hc ectodomain fitted nicely into the smaller density revealing the relative position of 4F2hc with respect to LAT2 and the membrane plane.

scholarly journals SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure

2019 ◽  
Vol 24 (9) ◽  
pp. 928-938 ◽  
Author(s):  
Luca Palazzolo ◽  
Chiara Paravicini ◽  
Tommaso Laurenzi ◽  
Sara Adobati ◽  
Simona Saporiti ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Amino Acid Residues ◽  
Dibasic Amino Acid ◽  
Novel Target ◽  
Function Relationship ◽  
Dynamics Simulations

SLC6A14 (ATB0,+) is a sodium- and chloride-dependent neutral and dibasic amino acid transporter that regulates the distribution of amino acids across cell membranes. The transporter is overexpressed in many human cancers characterized by an increased demand for amino acids; as such, it was recently acknowledged as a novel target for cancer therapy. The knowledge on the molecular mechanism of SLC6A14 transport is still limited, but some elegant studies on related transporters report the involvement of the 12 transmembrane α-helices in the transport mechanism, and describe structural rearrangements mediated by electrostatic interactions with some pivotal gating residues. In the present work, we constructed a SLC6A14 model in outward-facing conformation via homology modeling and used molecular dynamics simulations to predict amino acid residues critical for substrate recognition and translocation. We docked the proteinogenic amino acids and other known substrates in the SLC6A14 binding site to study both gating regions and the exposed residues involved in transport. Interestingly, some of these residues correspond to those previously identified in other LeuT-fold transporters; however, we could also identify a novel relevant residue with such function. For the first time, by combined approaches of molecular docking and molecular dynamics simulations, we highlight the potential role of these residues in neutral amino acid transport. This novel information unravels new aspects of the human SLC6A14 structure–function relationship and may have important outcomes for cancer treatment through the design of novel inhibitors of SLC6A14-mediated transport.

Seasonal variation in human amino acid excretion

1960 ◽  
Vol 15 (1) ◽  
pp. 121-124 ◽  
Author(s):  
Henry B. Hale ◽  
James P. Ellis ◽  
Donald D. Van Fossan
Keyword(s):  
Amino Acids ◽  
Seasonal Variation ◽  
Amino Acid ◽  
Glutamic Acid ◽  
Urine Volume ◽  
Urine Samples ◽  
Acid Excretion ◽  
Healthy Men ◽  
Significant Seasonal Variation ◽  
Sodium And Potassium

Amino acid excretion was studied in young, healthy men during summer, fall and winter months in a southwestern U. S. location. Both untimed and timed urine samples were employed. The amino acids determined were alanine, arginine, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methyl histidine, serine, threonine and valine. Supplemental determinations included urine volume, creatinine, uric acid, urea, sodium and potassium. Using untimed urine samples and expressing values as ratios with creatinine, significant seasonal variation was found for alanine, arginine, cysteine, glutamic acid, glycine, lysine and serine. Submitted on April 11, 1959

scholarly journals Hyaluronan-binding region of aggrecan from pig laryngeal cartilage. Amino acid sequence, analysis of N-linked oligosaccharides and location of the keratan sulphate

1992 ◽  
Vol 286 (3) ◽  
pp. 761-769 ◽  
Author(s):  
F P Barry ◽  
J U Gaw ◽  
C N Young ◽  
P J Neame
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Signal Peptidase ◽  
Amino Acid Residues ◽  
Terminal Sequence ◽  
Binding Region ◽  
Keratan Sulphate ◽  
Laryngeal Cartilage ◽  
Hyaluronan Binding

The hyaluronan-binding region (HABR) was prepared from pig laryngeal cartilage aggrecan and the amino acid sequence was determined. The HABR had two N-termini: one N-terminal sequence was Val-Glu-Val-Ser-Glu-Pro (367 amino acids in total), and a second N-terminal sequence (Ala-Ile-Ser-Val-Glu-Val; 370 amino acids in total) was found to arise due to alternate cleavage by the signal peptidase. The N-linked oligosaccharides were analysed by examining their reactivity with a series of lectins. It was found that the N-linked oligosaccharide on loop A was of the mannose type, while that on loop B was of the complex type. No reactivity was detected between the N-linked oligosaccharide on loop B' and any of the lectins. The location of keratan sulphate (KS) in the HABR was determined by Edman degradation of the immobilized KS-containing peptide. The released amino acid derivatives were collected and tested for the presence of epitope to antibody 5-D-4. On the basis of 5-D-4 reactivity and sequencing yields, the KS chains are attached to threonine residues 352 and 357. There is no KS at threonine-355. This site is not in fact in G1, but about 16 amino acid residues into the interglobular domain. Comparison of the structure of the KS chain from the HABR and from the KS domain of pig laryngeal cartilage aggrecan was made by separation on polyacrylamide gels of the oligosaccharides arising from digestion with keratanase. Comparison of the oligosaccharide maps suggests that the KS chains from both parts of the aggrecan molecule have the same structure.

ChemInform Abstract: β-Nitro-α-amino Acids as Latent α,β-Dehydro-α-amino Acid Residues in Peptides.

ChemInform ◽  
2010 ◽  
Vol 30 (34) ◽  
pp. no-no
Author(s):  
Phillip A. Coghlan ◽  
Christopher J. Easton
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Residues

Structure and function of the NHE1 isoform of the Na+/H+ exchanger

2002 ◽  
Vol 80 (5) ◽  
pp. 499-508 ◽  
Author(s):  
Emily Slepkov ◽  
Larry Fliegel
Keyword(s):  
Amino Acids ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Integral Membrane Protein ◽  
Amino Acid Residues ◽  
Transmembrane Helices ◽  
Cytoskeletal Organization ◽  
Transmembrane Segments ◽  
And Function ◽  
Extracellular Sodium

The Na+/H+ exchanger is a ubiquitous, integral membrane protein involved in pH regulation. It removes intracellular acid, exchanging a proton for an extracellular sodium ion. There are seven known isoforms of this protein that are the products of distinct genes. The first isoform discovered (NHE1) is ubiquitously distributed throughout the plasma membrane of virtually all tissues. It plays many different physiological roles in mammals, including important functions in regulation of intracellular pH, in heart disease, and in cytoskeletal organization. The first 500 amino acids of the protein are believed to consist of 12 transmembrane helices, a membrane-associated segment, and two reentrant loops. A C-terminal regulatory domain of approximately 315 amino acids regulates the protein and mediates cyto skel etal interactions. Studies are underway to determine the amino acid residues important in NHE1 function. At present, it is clear that transmembrane segment IV is important in NHE1 function and that transmembrane segments VII and IX are also involved in transport. Further experiments are required to elucidate the mechanism of transport and regulation of this multifunctional protein.Key words: cation transport, intracellular pH, membrane proteins, Na+/H+ exchanger.

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