Role of the loop L-4,L-5 in allosteric regulation in mtHsp70s: in vivo significance of domain communication and its implications in protein translocation

Mitochondrial Hsp70 (mtHsp70) is essential for a vast repertoire of functions, including protein import, and requires effective interdomain communication for efficient partner-protein interactions. However, the in vivo functional significance of allosteric regulation in eukaryotes is poorly defined. Using integrated biochemical and yeast genetic approaches, we provide compelling evidence that a conserved substrate-binding domain (SBD) loop, L-4,L-5, plays a critical role in allosteric communication governing mtHsp70 chaperone functions across species. In yeast, a temperature-sensitive L-4,L-5 mutation (E467A) disrupts bidirectional domain communication, leading to compromised protein import and mitochondrial function. Loop L-4,L-5 functions synergistically with the linker in modulating the allosteric interface and conformational transitions between SBD and the nucleotide-binding domain (NBD), thus regulating interdomain communication. Second-site intragenic suppressors of E467A isolated within the SBD suppress domain communication defects by conformationally altering the allosteric interface, thereby restoring import and growth phenotypes. Strikingly, the suppressor mutations highlight that restoration of communication from NBD to SBD alone is the minimum essential requirement for effective in vivo function when primed at higher basal ATPase activity, mimicking the J-protein-bound state. Together these findings provide the first mechanistic insights into critical regions within the SBD of mtHsp70s regulating interdomain communication, thus highlighting its importance in protein translocation and mitochondrial biogenesis.

Performance Evaluation of Underground Mine Communication and Monitoring Devices: Case Studies

Communication and environmental monitoring play a major role in underground mining both from production and safety point of view. However, underground mining communication as well as monitoring devices encounter several challenges because of the nature of underground features and characteristics. Lack of real time information from underground workings may hamper production and create serious safety risks. Proper communication and monitoring devices are inevitable requirements for better production and improved safety. Communication and environmental monitoring devices are basic element of underground mine infrastructure. This paper describes the performance of communication and monitoring devices being used in underground mines. An attempt has been made to assess the safety risks by these devices which may dictate future research directions.

Strategic Marketing and Innovation Performance of Indian MSMEs

Micro Small and Medium Enterprises (MSMEs) is an integral part of the Indian industrial sector. The distinctive features of MSMEs are less capital investment and high labour absorption which has created unprecedented importance to this sector. As per the Development Commissioner of MSME, the sector has the credit of being the second highest in employment in India, which stands next to agricultural sector. The MSMEs are very much needed in efficiently allocating the enormous labour supply and scarce capital by implementing labour intensive production processes. Associated with this high growth rates, MSMEs are also facing a number of problems like sub-optimal scale of operation, technological obsolescence, supply chain inefficiencies, increasing domestic and global competition, fund shortages, change in manufacturing & marketing strategies, turbulent and uncertain market scenario. To survive with such issues and compete with large and global enterprises, MSMEs need to adopt innovative approaches in their regular business operations. Among the manufacturing sectors, we find that they are unable to focus themselves in the present competition. This paper presents a brief literature of work done in MSMEs, Innovation and Strategic marketing with reference to Indian manufacturing firms.