Functional recycling of C2 domains throughout evolution: A comparative study of synaptotagmin, protein kinase C and phospholipase C by sequence, structural and modelling approaches

The C2 domain is one of the most frequent and widely distributed calcium-binding motifs. Its structure comprises an eight-stranded beta-sandwich with two structural types as if the result of a circular permutation. Combining sequence, structural and modelling information, we have explored, at different levels of granularity, the functional characteristics of several families of C2 domains. At the coarsest level,the similarity correlates with key structural determinants of the C2 domain fold and, at the finest level, with the domain architecture of the proteins containing them, highlighting the functional diversity between the various subfamilies. The functional diversity appears as different conserved surface patches throughout this common fold. In some cases, these patches are related to substrate-binding sites whereas in others they correspond to interfaces of presumably permanent interaction between other domains within the same polypeptide chain. For those related to substrate-binding sites, the predictions overlap with biochemical data in addition to providing some novel observations. For those acting as protein-protein interfaces' our modelling analysis suggests that slight variations between families are a result of not only complementary adaptations in the interfaces involved but also different domain architecture. In the light of the sequence and structural genomic projects, the work presented here shows that modelling approaches along with careful sub-typing of protein families will be a powerful combination for a broader coverage in proteomics. (C) 2003 Elsevier Ltd. All rights reserved.

A comparative analysis of entrepreneurial approaches within public healthcare organisations

This article examines the development of two distinct models of organising allied health professionals within two public sector health service organisations in Australia. The first case illustrated a mode of organising that facilitated a culture that focused on asset protection and whose external orientation was threat oriented because its disparate multiple identities operated as a fractured, fragmented and competitive set of profession disciplines. In this milieu, there was no evidence of entrepreneurial approaches being used. In contrast, the second case study illustrated a mode of organising that facilitated an entrepreneurial culture that focused on asset growth and an external orientation that was opportunity oriented because of the evolution of a strong superordinate allied health identity that operated as a single united health services stakeholder. This evolution was coupled with the emergence of a corporate boardroom model of management that is consonant with Savage et al. (1997) IDS/N model of management. Once this structure and strategy were in place, corporate entrepreneur ship became the modus operandi. Consequently, because the case study was a situation where corporate entrepreneurship existed in the public sector, it was possible to compare the factors that stimulate corporate entrepreneurship in Sadler's (2000) study with factors that were observed in our study.