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41.
Yoshida Y Suzuki K Yamamoto A Sakai N Bando M Tanimoto K Yamaguchi Y Sakaguchi T Akhter H Fujii G Yoshimura S Ogata S Sohda M Misumi Y Nakamura N 《Experimental cell research》2008,314(19):3427-3443
Yip1p/Yif1p family proteins are five-span transmembrane proteins localized in the Golgi apparatus and the ER. There are nine family members in humans, and YIPF5 and YIF1A are the human orthologs of budding yeast Yip1p and Yif1p, respectively. We raised antisera against YIPF5 and YIF1A and examined the localization of endogenous proteins in HeLa cells. Immunofluorescence, immunoelectron microscopy and subcellular fractionation analysis suggested that YIPF5 and YIF1A are not restricted to ER exit sites but also localized in the ER-Golgi intermediate compartment (ERGIC) and some in the cis-Golgi at steady state. Along with ERGIC53, YIPF5 and YIF1A remained in the cytoplasmic punctate structures after brefeldin A treatment, accumulated in the ERGIC and the cis-Golgi after treatment with AlF4- and accumulated in the ER when ER to Golgi transport was inhibited by Sar1(H79G). These results supported the localization of YIPF5 and YIF1A in the ERGIC and the cis-Golgi, and strongly suggested that they are recycling between the ER and the Golgi apparatus. Analysis by blue native PAGE and co-immunoprecipitation showed that YIPF5 and YIF1A form stable complexes of three different sizes. Interestingly, the knockdown of YIPF5 or YIF1A caused partial disassembly of the Golgi apparatus suggesting that YIPF5 and YIF1A are involved in the maintenance of the Golgi structure. 相似文献
42.
43.
Peptidomimetics are designed to overcome the poor pharmacokinetics and pharmacodynamics associated with the native peptide or protein on which they are based. The design of peptidomimetics starts from developing structure-activity relationships of the native ligand-target pair that identify the key residues that are responsible for the biological effect of the native peptide or protein. Then minimization of the structure and introduction of constraints are applied to create the core active site that can interact with the target with high affinity and selectivity. Developing peptidomimetics is not trivial and often challenging, particularly when peptides’ interaction mechanism with their target is complex. This review will discuss the challenges of developing peptidomimetics of therapeutically important insulin superfamily peptides, particularly those which have two chains (A and B) and three disulfide bonds and whose receptors are known, namely insulin, H2 relaxin, H3 relaxin, INSL3 and INSL5. 相似文献
44.
From mutations to mechanisms and dysfunction via computation and mining of protein energy landscapes
Qiao Wanli Akhter Nasrin Fang Xiaowen Maximova Tatiana Plaku Erion Shehu Amarda 《BMC genomics》2018,19(7):671-13
Background
The protein energy landscape underscores the inherent nature of proteins as dynamic molecules interconverting between structures with varying energies. Reconstructing a protein’s energy landscape holds the key to characterizing a protein’s equilibrium conformational dynamics and its relationship to function. Many pathogenic mutations in protein sequences alter the equilibrium dynamics that regulates molecular interactions and thus protein function. In principle, reconstructing energy landscapes of a protein’s healthy and diseased variants is a central step to understanding how mutations impact dynamics, biological mechanisms, and function.Results
Recent computational advances are yielding detailed, sample-based representations of protein energy landscapes. In this paper, we propose and describe two novel methods that leverage computed, sample-based representations of landscapes to reconstruct them and extract from them informative local structures that reveal the underlying organization of an energy landscape. Such structures constitute landscape features that, as we demonstrate here, can be utilized to detect alterations of landscapes upon mutation.Conclusions
The proposed methods detect altered protein energy landscape features in response to sequence mutations. By doing so, the methods allow formulating hypotheses on the impact of mutations on specific biological activities of a protein. This work demonstrates that the availability of energy landscapes of healthy and diseased variants of a protein opens up new avenues to harness the quantitative information embedded in landscapes to summarize mechanisms via which mutations alter protein dynamics to percolate to dysfunction.45.
FcɛR1α gene polymorphism shows association with high IgE and anti‐FcɛR1α in Chronic Rhinosinusitis with Nasal Polyposis
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46.
Comparative proteome analysis reveals pathogen specific outer membrane proteins of Leptospira
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Aarti Rana Rahul Brahma Yusuf Akhter Madathiparambil Gopalakrishnan Madanan 《Proteins》2018,86(7):712-722
Proteomes of pathogenic Leptospira interrogans and L. borgpetersenii and the saprophytic L. biflexa were filtered through computational tools to identify Outer Membrane Proteins (OMPs) that satisfy the required biophysical parameters for their presence on the outer membrane. A total of 133, 130, and 144 OMPs were identified in L. interrogans, L. borgpetersenii, and L. biflexa, respectively, which forms approximately 4% of proteomes. A holistic analysis of transporting and pathogenic characteristics of OMPs together with Clusters of Orthologous Groups (COGs) among the OMPs and their distribution across 3 species was made and put forward a set of 21 candidate OMPs specific to pathogenic leptospires. It is also found that proteins homologous to the candidate OMPs were also present in other pathogenic species of leptospires. Six OMPs from L. interrogans and 2 from L. borgpetersenii observed to have similar COGs while those were not found in any intermediate or saprophytic forms. These OMPs appears to have role in infection and pathogenesis and useful for anti‐leptospiral strategies. 相似文献
47.
D. W. Lee Steven F. Oberbauer Baskaran Krishnapilay Marzalina Mansor Haris Mohamad Son Kheong Yap 《Oecologia》1997,110(1):1-9
Seedling developmental responses to understory shade combine the effects of reductions in irradiance and changes in spectral
quality. We studied the seedling development of two Southeast Asian dipterocarp trees in response to differences in irradiance
(photosynthetic photon flux density, PPFD) and spectral quality (red to far-red ratio, R:FR). The two species, Hopea helferei and H. odorata, are taxonomically closely related but differ in their ecological requirements; H. helferei is more drought-tolerant and typically grows in more open habitats. Seedlings were grown in six different replicated shadehouse
treatments varying in percentage of solar PPFD and R:FR. The two species differed in the influence of light variables on most
seedling characters, particularly for final height, internode distance, branch/trunk internodes, stem length/mass, leaf area/stem
length, petiole length, and growth/mol of photons received. Most of the characters in both taxa were primarily influenced
by PPFD, but spectral quality also influenced some characters – more so for H. odorata. The latter species grew more rapidly, particularly in the low PPFD treatments, and its leaves were capable of higher photosynthesis
rates. However, growth in H. helferei was not reduced in direct sunlight. The growth of this taxon may be constrained by adaptations, particularly in leaves, for
drought tolerance.
Received: 14 April 1996 / Accepted: 8 October 1996 相似文献
48.
Mohammed Akhter Hossain Fabrice Thomas Sylvain Hamman Eric Saint-Aman Didier Boturyn Pascal Dumy Jean-Louis Pierre 《Journal of peptide science》2006,12(9):612-619
Tyrosyl radicals are involved in many biologically important processes. The development of model compounds to mimic radical enzyme active sites, such as galactose oxidase (GO), has widely contributed to an enhanced understanding of their spectral properties, structural attributes and even reactivity. An emerging approach towards the synthesis of such active site mimetics is the use of peptidic ligands. The potential of cyclodecapeptides to bear phenoxyl radicals has been evaluated through three compounds. LH(4) (2+) is a cyclodecapetide containing two histidine residues (mimicking His(496) and His(581) of GO) and two tyrosine residues (mimicking Tyr(495) and the Tyr(272)* radical of GO). L(tBu)H(4) (2+) and L(OMe)H(4) (2+) incorporate 2,4,6-protected phenols in place of each tyrosine in LH(4) (2+). The deprotonation constants of each peptide determined by potentiometric titrations showed that there are some interactions between the acido-basic residues. Cyclic voltammetric studies revealed that only the peptides incorporating 2,4,6-protected phenolates exhibit reversible redox couples and are thus precursors of radicals stable enough to persist in solution. These studies also showed L(OMe2-) to possess the lower oxidation potential, indicating that this peptide, in its radical form, is the most stabilized. The electrochemically generated radical species have been characterized by EPR spectroscopy. 相似文献
49.
The demand for cloud computing is increasing dramatically due to the high computational requirements of business, social, web and scientific applications. Nowadays, applications and services are hosted on the cloud in order to reduce the costs of hardware, software and maintenance. To satisfy this high demand, the number of large-scale data centers has increased, which consumes a high volume of electrical power, has a negative impact on the environment, and comes with high operational costs. In this paper, we discuss many ongoing or implemented energy aware resource allocation techniques for cloud environments. We also present a comprehensive review on the different energy aware resource allocation and selection algorithms for virtual machines in the cloud. Finally, we come up with further research issues and challenges for future cloud environments. 相似文献
50.
Fahd Al-Mulla Mahera Abdulrahman Govindarajulu Varadharaj Nadeem Akhter Jehoram T Anim 《The journal of histochemistry and cytochemistry》2005,53(5):621-629
Breast cancer is a major cause of cancer-related mortality in women. There are major discrepancies concerning the usefulness of various antibodies in detecting breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular localization. The aim of the present study was to determine the specificity and sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast cancer tissues was studied simultaneously at the protein and mRNA levels, and the two findings were compared. Forty-eight archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression at protein level by IHC using four different antibodies against different BRCA1 epitopes and at mRNA level using real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the samples, and this finding correlated significantly with loss of BRCA1 protein expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB-1, against N-terminus epitope). The specificity of this antibody was 91.3%, and its sensitivity was 66.6%. There was no significant correlation between BRCA1 mRNA and protein expression as demonstrated by the remaining three antibodies. Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4% if mRNA levels were considered as the reference standard. 相似文献