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Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg2.39, His2.43 and Glu3.46, which makes a polar lock with T6.37. These alignments and models provide useful tools for understanding class B GPCR function.  相似文献   
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These notes outline tribological research effort in Japan, giving emphasis to applications to engineering practice. The author indicates the value of a freer exchange of information between Japanese workers and the rest of the world.  相似文献   
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These notes outline tribological research effort in Japan, giving emphasis to applications to engineering practice. The author indicates the value of a freer exchange of information between Japanese workers and the rest of the world.  相似文献   
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Many machine elements embody interacting surfaces which are counterformal thus causing concentration of stress on to a small area. Failure of such elements may occur due to excessive Hertzian stress leading to plastic deformation, surface disintegration, fatigue, or thermal distress (scuffing). The implications of recent research, notably that on elastohydrodynamic lubrication, are discussed and the need for specifying reliability at the outset of the design process is emphasized. Considerable progress has been made in applying the concept of elastohydrodynamic lubrication to the rating of rolling-contact bearings but there is still much scope for more precise methods. Particular attention should be paid to changes in surface texture during running-in and their possible effect on fatigue.  相似文献   
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