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H Peled

Publications and source records attributed to H Peled.

6 recordsLinked to original sources

Synthetic S-2 and H-5 segments of the Shaker K+ channel: secondary structure, membrane interaction, and assembly within phospholipid membranes.

Current models of voltage-activated K+ channels predict that the channels are formed by the coassembly of four polypeptide monomers, each of which consists of six transmembrane segments (S1-S6) and long terminal domains. The aqueous pores are thought to be composed of the conserved H-5 regions contributed by four monomers. In this study, two putative membrane-embedded segments of the Shaker K+ channel were synthesized. One segment corresponds to the putative, transmembrane helix S-2 (amino acids 275-300), and the other corresponds to the highly conserved 12 amino acid residues within the H-5 region [amino acids 432-443, designated (12)H-5]. Structural and functional characterization at elevated lipid/peptide molar ratios (> 3000:1) was performed on the two segments, as well as on a previously synthesized 21 amino acid long peptide with a sequence resembling the entire H-5 region (designated (21)H-5) (Peled & Shai, 1993). Circular dichroism spectroscopy revealed that S-2 adopts predominantly alpha-helical structure in both trifluoroethanol and 35 mM SDS (78% or 99%, respectively), while (12)H-5 and (21)H-5 adopt low alpha-helical structure only in the presence of 35 mM SDS. Functional characterization demonstrated that S-2 and (12)H-5 segments bind to zwitterionic phospholipids, with partition coefficients on the order of 10(4) M-1. Resonance energy transfer measurements, between donor/acceptor-labeled pairs of peptides, revealed that the peptides self-associate in their membrane-bound state, which may correlate with the existence of functional interactions between the conserved (12)H-5 regions of different subunits of K+ channels (Kirsch et al., 1993).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Membrane interaction and self-assembly within phospholipid membranes of synthetic segments corresponding to the H-5 region of the shaker K+ channel.

The voltage-activated K+ channels are assumed to be formed by the coassembly of four polypeptide monomers. Each of these monomers is postulated to consist of six transmembrane segments (S1 to S6), and long N- and C-terminal domains. The highly conserved linker, H-5, between the fifth and the sixth transmembrane segments, is hypothesized to line the lumen of the K+ channel formed by the bundle of the transmembrane segments of the monomers. Herein we utilize the spectrofluorometric approach and investigate the interaction with phospholipid membranes of fluorescently-labeled synthetic peptides, whose sequences are derived from the H-5 region. Binding experiments reveal that the peptides can strongly bind to phospholipid membranes with partition coefficients on the order of 10(4) M-1. However, a truncated peptide without four amino acids within the most conserved region (amino acids 432-435) did not bind to the membranes at all. Moreover, the single substitution of a conserved tryptophan at position 435 to serine reduced the partition coefficient of the peptide approximately 5-fold, which may account for a mutated K+ channel with this substitution not producing functional channels (Yool & Schwarz, 1991). Structural characterization using circular dichroism spectroscopy (CD) reveals that H-5 can partially adopt an alpha-helix structure in hydrophobic environments. Resonance energy transfer (RET) experiments reveal that the H-5-derived segments can self-assemble within the membrane but cannot coassemble with other unrelated membrane-bound peptides. The results herein support the hypothesis that H-5 segments are packed in close proximity and might participate in mediating the appropriate assembly of the core region of K+ channel monomers.

Amino Acid Sequence↗

Atrial infarction: diagnosis and management.

Atrial infarction has been a relatively understudied entity. Its incidence by autopsy study has been widely variable, from 0.7% to 42%, with the largest series of 182 patients demonstrating an incidence of 17%. The right atrium is involved five times as often as the left, with the auricle the predominant site in either atria. Clinical atrial infarction may present with supraventricular arrhythmias, atrial rupture, hemodynamic compromise from loss of atrial "kick," and thromboembolic phenomena. Diagnosis currently is made in an appropriate clinical setting with characteristic PR interval changes. Other noninvasive techniques have shown only limited diagnostic utility, but esophageal echocardiography may prove to be a useful technique in this setting.

Arrhythmias, Cardiac↗

Calcium channel blockers in systemic hypertension.

Alterations in transmembrane flux of calcium ions may be playing a role in the pathophysiology of systemic hypertension. Calcium channel blockers have been shown to be effective antihypertensive drugs with excellent safety profiles. They are efficacious in the long term treatment of systemic hypertension in all population subgroups, and have special applicability for treating patients with hypertensive urgencies and individuals with concomitant diseases such as angina pectoris and arrhythmias.

Animals↗

The Gulf War: pediatric emergency room function.

PURPOSE: To analyze the effects of war on the civilian population through patterns of medical service consumption in a pediatric emergency room. METHODOLOGY: A survey of variables related to use of emergency room services before, during, and after the Gulf War. RESULTS: There was a dramatic decrease in the number of visits during the war. During the war, there were fewer visits for URI, home accidents and intoxications; there were more visits for complaints such as headaches, restlessness, and tremors. CONCLUSIONS: Visits during the ware were more related to emergency situations with fewer visits of the walk-in clinic type.

Adolescent↗