Key Elements Of Structure Research Articles

Properties of Rab5 N-terminal domain dictate prenylation of C-terminal cysteines.

Rab5 is a Ras-related GTP-binding protein that is post-translationally modified by prenylation. We report here that an N-terminal domain contained within the first 22 amino acids of Rab5 is critical for efficient geranylgeranylation of the protein's C-terminal cysteines. This domain is immediately upstream from the "phosphate binding loop" common to all GTP-binding proteins and contains a highly conserved sequence recognized among members of the Rab family, referred to here as the YXYLFK motif. A truncation mutant that lacks this domain (Rab5(23-215) fails to become prenylated. However, a chimeric peptide with the conserved motif replacing cognate Rab5 sequence (MAYDYLFKRab5(23-215) does become post-translationally modified, demonstrating that the presence of this simple six amino acid N-terminal element enables prenylation at Rab5's C-terminus. H-Ras/Rab5 chimeras that include the conserved YXYLFK motif at the N-terminus do not become prenylated, indicating that, while this element may be necessary for prenylation of Rab proteins, it alone is not sufficient to confer properties to a heterologous protein to enable substrate recognition by the Rab geranylgeranyl transferase. Deletion analysis and studies of point mutants further reveal that the lysine residue of the YXYLFK motif is an absolute requirement to enable geranylgeranylation of Rab proteins. Functional studies support the idea that this domain is not required for guanine nucleotide binding since prenylation-defective mutants still bind GDP and are protected from protease digestion in the presence of GTP gamma S. We conclude that the mechanism of Rab geranylgeranylation involves key elements of the protein's tertiary structure including a conserved N-terminal amino acid motif (YXYLFK) that incorporates a critical lysine residue.

The evolution of the mantle's chemical structure

The geochemistry of flood basalts and their associated picrites, and of komatiites and their associated basalts, combined with a theoretical model for the structure of mantle starting plumes, can be used to decipher key elements of the geochemical structure of the deep mantle and show how it has varied through time. We argue that the thermal boundary layer above the core consisted mainly of depleted mantle similar to the present MORB source during the Archaean and this was largely replaced between 2.7 and 2.0 billion years ago by enriched mantle to form the OIB source. We suggest that this change in the nature of the hotspot source reflects a fundamental change in the dominant component of downward convection: from cold plumes breaking away from beneath a stable lithosphere during the pre-Archaean to subduction of lithosphere in the Archaean and post-Archaean mantles.

Retail spending patterns 1961–81

The EDC for the Distributive Trades has recently published “Retail Trade Prospects” by C.B. Moir, on the development of key elements in retail trade structure in the UK over the period 1961–81. This report is the first stage of a triple series including a second report on the labour structure in distribution, and a final synthesis on the employment prospects for the distributive trades to 1987. Montague Lewis summarises the report and comments personally on the results and indications of future prospects for the distributive trades.

Reimbursement for nondistributive pharmaceutical services in hospitals

The literature on reimbursement, especially by third-party payers, for clinical pharmacy services is reviewed. Allocation of total departmental expenses on a per-dose basis, subsidization of clinical pharmacy services through general pharmacy revenues, and inclusion of service charges with drug-product charges have been used successfully to support clinical services. Identification and documentation of benefits resulting from clinical pharmacy services is a vital element in the justification process; a new service has little chance for approval unless it documents cost savings. Published reports of clinical pharmacy services that obtained third-party reimbursement include programs in a cardiac-rehabilitation unit, patient education and monitoring, pharmacokinetics, and laboratory-results interpretation. Published guidelines for obtaining reimbursement for clinical pharmacy services are reviewed. An eight-point guide for obtaining reimbursement is recommended. It embodies: a commitment by the director of pharmacy, via departmental goals and objectives, to clinical services; presentation and acceptance by various key elements in a hospital's structure; accurate analysis of costs and benefits associated with the services; requests for reimbursement from third-party payers; continued analysis of the services' effects; and communication of experience with the services to the general public and the pharmacy profession. It is concluded that reimbursement by third-party payers is a step in the right direction and that clinical service charges should be separated from product charges. Further program development and research are needed.