Biophysics (Nagoya-shi, Japan)最新文献

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Role of TRP channels in the induction of heat shock proteins (Hsps) by heating skin. TRP通道在加热皮肤诱导热休克蛋白(Hsps)中的作用。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-02-13 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.25
Wen-Li Hsu, Tohru Yoshioka
{"title":"Role of TRP channels in the induction of heat shock proteins (Hsps) by heating skin.","authors":"Wen-Li Hsu,&nbsp;Tohru Yoshioka","doi":"10.2142/biophysics.11.25","DOIUrl":"https://doi.org/10.2142/biophysics.11.25","url":null,"abstract":"<p><p>Transient receptor potential (TRP) channels in skin are crucial for achieving temperature sensitivity to maintain internal temperature balance and thermal homeostasis, as well as to protect skin cells from environmental stresses such as infrared (IR) or near-infrared (NIR) radiation via heat shock protein (Hsp) production. However, the mechanisms by which IR and NIR activate TRP channels and produce Hsps intracellularly have been independently reported. In this review, we discuss the relationship between TRP channel activation and Hsp production, and introduce the roles of several skin TRP channels in the regulation of HSP production by IR and NIR exposure. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.11.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34344149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Thermodynamic implications of high Q 10 of thermo-TRP channels in living cells. 活细胞中热-TRP 通道高 Q 10 的热力学影响。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-02-13 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.33
Etsuro Ito, Yusuke Ikemoto, Tohru Yoshioka
{"title":"Thermodynamic implications of high Q 10 of thermo-TRP channels in living cells.","authors":"Etsuro Ito, Yusuke Ikemoto, Tohru Yoshioka","doi":"10.2142/biophysics.11.33","DOIUrl":"10.2142/biophysics.11.33","url":null,"abstract":"<p><p>The activity of thermo-transient receptor potential (TRP) channels is highly dependent on temperature, and thus thermo-TRP reactions have a high temperature coefficient Q 10. In thermodynamics, a high value of Q 10 indicates the existence of a large activation energy (i.e., a large enthalpy) over a short period during the transition process between the closed and open states of the channels. The Gibbs free energy equation shows that a large entropy is required to compensate for this large enthalpy and permit activation of the channels, suggesting a large conformational change of the channels. These large values of enthalpy and entropy seem to be a match for the values of the unfolding process of globular proteins. We outline these thermodynamic issues in thermo-TRPs. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"33-8"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34344150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FTIR study of CPD photolyase with substrate in single strand DNA. 单链DNA底物CPD光解酶的FTIR研究。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-02-13 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.39
I M Mahaputra Wijaya, Tatsuya Iwata, Junpei Yamamoto, Kenichi Hitomi, Shigenori Iwai, Elizabeth D Getzoff, Hideki Kandori
{"title":"FTIR study of CPD photolyase with substrate in single strand DNA.","authors":"I M Mahaputra Wijaya,&nbsp;Tatsuya Iwata,&nbsp;Junpei Yamamoto,&nbsp;Kenichi Hitomi,&nbsp;Shigenori Iwai,&nbsp;Elizabeth D Getzoff,&nbsp;Hideki Kandori","doi":"10.2142/biophysics.11.39","DOIUrl":"https://doi.org/10.2142/biophysics.11.39","url":null,"abstract":"<p><p>Photolyases (PHRs) utilize near UV/blue light to specifically repair the major photoproducts (PPs) of UV-induced damaged DNA. The cyclobutane pyrimidine dimer (CPD)-PHR binds flavin adenine dinucleotide (FAD) as a cofactor and repairs CPD lesions in double-stranded DNA. To understand the activation and repair mechanism of CPD-PHR, we applied light-induced difference Fourier transform infrared (FTIR) spectroscopy to CPD-PHR, whose signals were identified by use of isotope-labeling. To further investigate the enzymatic function, here we study the activation and repair mechanism of CPD-PHR with the substrate in single strand DNA, and the obtained FTIR spectra are compared with those in double-stranded DNA, the natural substrate. The difference spectra of photoactivation, the fully-reduced (FADH(-)) minus semiquinone (FADH(•)) spectra, are almost identical in the presence of single strand and double-stranded DNA, except for slight spectral modification in the amide-I region. On the other hand, the difference spectra of photorepair were highly substrate dependent. Strong bands of the C=O stretch (1,720-1,690 cm(-1)) and phosphate vibrations (1,090-1,060 cm(-1)) of double-stranded DNA may have disappeared in the case of single strand DNA. However, an isotope-labeled enzyme study revealed that spectral features upon DNA repair are similar between both substrates, and the main reason for the apparent spectral difference originates from structural flexibility of DNA after repair. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"39-45"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.11.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34344151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons. 表达ib4阴性trpv1的肌肉传入DRG神经元的电生理特征。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-02-13 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.9
Yi-Wen Lin, Chih-Cheng Chen
{"title":"Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons.","authors":"Yi-Wen Lin,&nbsp;Chih-Cheng Chen","doi":"10.2142/biophysics.11.9","DOIUrl":"https://doi.org/10.2142/biophysics.11.9","url":null,"abstract":"<p><p>Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acid-induced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole-cell patch clamp recording to study the acid responsiveness and action potential (AP) configuration of capsaicin-sensitive neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size, resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and acid-induced current (I acid), as well as capsaicin-induced current (I cap). TRPV1-expressing neurons were all acid-sensitive and could be divided into two acid-sensitive groups depending on an acid-induced sustained current (type I) or an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing neurons were distinguishable from type II TRPV1-expressing neurons in AP overshoot, after-hyperpolarization duration, and all I acid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and I cap parameters. These differential biophysical properties of TRPV1-expressing neurons might partially annotate their different roles involved in the development and maintenance of chronic muscle pain. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"9-16"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.11.9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34344147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
TRP channels in skin: from physiological implications to clinical significances. 皮肤中的TRP通道:从生理意义到临床意义。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-02-13 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.17
Ji-Chen Ho, Chih-Hung Lee
{"title":"TRP channels in skin: from physiological implications to clinical significances.","authors":"Ji-Chen Ho,&nbsp;Chih-Hung Lee","doi":"10.2142/biophysics.11.17","DOIUrl":"https://doi.org/10.2142/biophysics.11.17","url":null,"abstract":"<p><p>TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"17-24"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.11.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34344148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 35
Effects of serotonin on the heartbeat of pond snails in a hunger state. 血清素对饥饿状态塘螺心跳的影响。
Biophysics (Nagoya-shi, Japan) Pub Date : 2015-01-05 eCollection Date: 2015-01-01 DOI: 10.2142/biophysics.11.1
Miki Yamagishi, Takayuki Watanabe, Dai Hatakeyama, Etsuro Ito
{"title":"Effects of serotonin on the heartbeat of pond snails in a hunger state.","authors":"Miki Yamagishi,&nbsp;Takayuki Watanabe,&nbsp;Dai Hatakeyama,&nbsp;Etsuro Ito","doi":"10.2142/biophysics.11.1","DOIUrl":"https://doi.org/10.2142/biophysics.11.1","url":null,"abstract":"<p><p>Serotonin (5-hydroxytryptamine: 5-HT) is a multimodal transmitter that controls both feeding response and heartbeat in snails. However, the effects of 5-HT on the hunger state are still unknown. We therefore examined the relation among the hunger state, the heartbeat rate and the 5-HT action in food-starved snails. We found that the hunger state was significantly distinguished by the heartbeat rate in snails. The heartbeat rate was high in the food-satiated snails, whereas it was low in the food-starved snails. An increase in 5-HT concentration in the body boosted the heartbeat rate in the food-starved snails, but did not affect the rate in the food-satiated snails. These results suggest that 5-HT application may mimic the change from a starvation to a satiation state normally achieved by direct ingestion of food. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"11 ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.11.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34734071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Electrophysiological characteristics of feeding-related neurons after taste avoidance Pavlovian conditioning in Lymnaea stagnalis. 盲蝽味觉回避巴甫洛夫条件反射后进食相关神经元的电生理特征。
Biophysics (Nagoya-shi, Japan) Pub Date : 2014-12-25 eCollection Date: 2014-01-01 DOI: 10.2142/biophysics.10.121
Hiroshi Sunada, Satoshi Takigami, Ken Lukowiak, Manabu Sakakibara
{"title":"Electrophysiological characteristics of feeding-related neurons after taste avoidance Pavlovian conditioning in Lymnaea stagnalis.","authors":"Hiroshi Sunada,&nbsp;Satoshi Takigami,&nbsp;Ken Lukowiak,&nbsp;Manabu Sakakibara","doi":"10.2142/biophysics.10.121","DOIUrl":"https://doi.org/10.2142/biophysics.10.121","url":null,"abstract":"<p><p>Taste avoidance conditioning (TAC) was carried out on the pond snail, Lymnaea stagnalis. The conditional stimulus (CS) was sucrose which elicits feeding behavior; while the unconditional stimulus (US) was a tactile stimulus to the head which causes feeding to be suppressed. The neuronal circuit that drives feeding behavior in Lymnaea is well worked out. We therefore compared the physiological characteristics on 3 classes of neurons involved with feeding behavior especially in response to the CS in conditioned vs. control snails. The cerebral giant cell (CGC) modulates feeding behavior, N1 medial neuron (N1M) is one of the central pattern generator neurons that organizes feeding behavior, while B3 is a motor neuron active during the rasp phase of feeding. We found the resting membrane potential in CGC was hyperpolarized significantly in conditioned snails but impulse activity remained the same between conditioned vs. control snails. There was, however, a significant increase in spontaneous activity and a significant depolarization of N1M's resting membrane potential in conditioned snails. These changes in N1M activity as a result of training are thought to be due to withdrawal interneuron RPeD11 altering the activity of the CGCs. Finally, in B3 there was: 1) a significant decrease in the amplitude and the frequency of the post-synaptic potentials; 2) a significant hyperpolarization of resting membrane potential in conditioned snails; and 3) a disappearance of bursting activity typically initiated by the CS. These neuronal modifications are consistent with the behavioral phenotype elicited by the CS following conditioning. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"10 ","pages":"121-33"},"PeriodicalIF":0.0,"publicationDate":"2014-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.10.121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34734070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Cooperation between phenotypic plasticity and genetic mutations can account for the cumulative selection in evolution. 表型可塑性和基因突变之间的合作可以解释进化中的累积选择。
Biophysics (Nagoya-shi, Japan) Pub Date : 2014-12-17 eCollection Date: 2014-01-01 DOI: 10.2142/biophysics.10.99
Ken Nishikawa, Akira R Kinjo
{"title":"Cooperation between phenotypic plasticity and genetic mutations can account for the cumulative selection in evolution.","authors":"Ken Nishikawa,&nbsp;Akira R Kinjo","doi":"10.2142/biophysics.10.99","DOIUrl":"https://doi.org/10.2142/biophysics.10.99","url":null,"abstract":"<p><p>We propose the cooperative model of phenotype-driven evolution, in which natural selection operates on a phenotype caused by both genetic and epigenetic factors. The conventional theory of evolutionary synthesis assumes that a phenotypic value (P) is the sum of genotypic value (G) and environmental deviation (E), P=G+E, where E is the fluctuations of the phenotype among individuals in the absence of environmental changes. In contrast, the cooperative model assumes that an evolution is triggered by an environmental change and individuals respond to the change by phenotypic plasticity (epigenetic changes). The phenotypic plasticity, while essentially qualitative, is denoted by a quantitative value F which is modeled as a normal random variable like E, but with a much larger variance. Thus, the fundamental equation of the cooperative model is given as P=G+F where F includes the effect of E. Computer simulations using a genetic algorithm demonstrated that the cooperative model realized much faster evolution than the evolutionary synthesis. This accelerated evolution was found to be due to the cumulative evolution made possible by a ratchet mechanism due to the epigenetic contribution to the phenotypic value. The cooperative model can well account for the phenomenon of genetic assimilation, which, in turn, suggests the mechanism of cumulative selection. The cooperative model may also serve as a theoretical basis to understand various ideas and phenomena of the phenotype-driven evolution such as genetic assimilation, the theory of facilitated phenotypic variation, and epigenetic inheritance over generations. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"10 ","pages":"99-108"},"PeriodicalIF":0.0,"publicationDate":"2014-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.10.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34734068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts. 单WI-38成纤维细胞显微热脉冲诱导的钙动力学。
Biophysics (Nagoya-shi, Japan) Pub Date : 2014-12-17 eCollection Date: 2014-01-01 DOI: 10.2142/biophysics.10.109
Hideki Itoh, Kotaro Oyama, Madoka Suzuki, Shin'ichi Ishiwata
{"title":"Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts.","authors":"Hideki Itoh,&nbsp;Kotaro Oyama,&nbsp;Madoka Suzuki,&nbsp;Shin'ichi Ishiwata","doi":"10.2142/biophysics.10.109","DOIUrl":"https://doi.org/10.2142/biophysics.10.109","url":null,"abstract":"<p><p>Temperature-sensitive Ca(2+) dynamics occur primarily through transient receptor potential channels, but also by means of Ca(2+) channels and pumps on the endoplasmic reticulum membrane. As such, cytoplasmic Ca(2+) concentration ([Ca(2+)]cyt) is re-equilibrated by changes in ambient temperature. The present study investigated the effects of heat pulses (heating duration: 2 s or 150 s) on [Ca(2+)]cyt in single WI-38 fibroblasts, which are considered as normal cells. We found that Ca(2+) burst occurred immediately after short (2 s) heat pulse, which is similar to our previous report on HeLa cells, but with less thermosensitivity. The heat pulses originated from a focused 1455-nm infrared laser light were applied in the vicinity of cells under the optical microscope. Ca(2+) bursts induced by the heat pulse were suppressed by treating cells with inhibitors for sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) or inositol trisphosphate receptor (IP3R). Long (150 s) heat pulses also induced Ca(2+) bursts after the onset of heating and immediately after re-cooling. Cells were more thermosensitive at physiological (37°C) than at room (25°C) temperature; however, at 37°C, cells were responsive at a higher temperature (ambient temperature+heat pulse). These results strongly suggest that the heat pulse-induced Ca(2+) burst is caused by a transient imbalance in Ca(2+) flow between SERCA and IP3R, and offer a potential new method for thermally controlling Ca(2+)-regulated cellular functions. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"10 ","pages":"109-19"},"PeriodicalIF":0.0,"publicationDate":"2014-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2142/biophysics.10.109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34734069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
3-D structural analysis of the crucial intermediate of skeletal muscle myosin and its role in revised actomyosin cross-bridge cycle. 骨骼肌肌球蛋白关键中间体的三维结构分析及其在修正的肌动蛋白横桥循环中的作用。
Biophysics (Nagoya-shi, Japan) Pub Date : 2014-11-12 eCollection Date: 2014-01-01 DOI: 10.2142/biophysics.10.89
Eisaku Katayama
{"title":"3-D structural analysis of the crucial intermediate of skeletal muscle myosin and its role in revised actomyosin cross-bridge cycle.","authors":"Eisaku Katayama","doi":"10.2142/biophysics.10.89","DOIUrl":"10.2142/biophysics.10.89","url":null,"abstract":"<p><p>Skeletal myosin S1 consists of two functional segments, a catalytic-domain and a lever-arm. Since the crystal structure of ADP/Vi-bound S1 exhibits a strong intramolecular flexure between two segments, inter-conversion between bent and extended forms; i.e. \"tilting of the lever-arm\" has been accepted as the established molecular mechanism of skeletal muscle contraction. We utilized quick-freeze deep-etch replica electron microscopy to directly visualize the structure of in vitro actin-sliding myosin, and found the existence of a novel oppositely-bent configuration, instead of the expected ADP/Vi-bound form. We also noticed that SH1-SH2 cross-linked myosin gives an aberrant appearance similar to the above structure. Since SH1-SH2-cross-linked myosin is a well-studied analogue of the transient intermediate of the actomyosin cross-bridge cycle, we devised a new image-processing procedure to define the relative view-angles between the catalytic-domain and the lever-arm from those averaged images, and built a 3-D model of the new conformer. The lever-arm in that model was bent oppositely to the ADP/Vi-bound form, in accordance with observed actin-sliding cross-bridge structure. Introducing this conformer as the crucial intermediate that transiently appears during sliding, we propose a revised scheme of the cross-bridge cycle. In the scenario, the novel conformer keeps actin-binding in two different modes until it forms a primed configuration. The final extension of the lever-arm back to the original rigor-state constitutes the \"power-stroke\". Various images observed during sliding could be easily interpreted by the new conformer. Even the enigmatic behavior of the cross-bridges reported as \"loose chemo-mechanical coupling\" might be adequately explained under some assumptions. </p>","PeriodicalId":91456,"journal":{"name":"Biophysics (Nagoya-shi, Japan)","volume":"10 ","pages":"89-97"},"PeriodicalIF":0.0,"publicationDate":"2014-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34734067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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