			Home About us Contact

Distal Loop (distal + loop)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2005
M. D. Säemann
Abstract Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria. [source]

Backbone dynamics of the human MIA protein studied by 15N NMR relaxation: Implications for extended interactions of SH3 domains

PROTEIN SCIENCE, Issue 3 2003
Raphael Stoll
MIA, melanoma inhibitory activity; NMR, nuclear magnetic resonance Abstract The melanoma inhibitory activity (MIA) protein is a clinically valuable marker in patients with malignant melanoma as enhanced values diagnose metastatic melanoma stages III and IV. Here, we report the backbone dynamics of human MIA studied by 15N NMR relaxation experiments. The folded core of human MIA is found to be rigid, but several loops connecting ,-sheets, such as the RT-loop for example, display increased mobility on picosecond to nanosecond time scales. One of the most important dynamic features is the pronounced flexibility of the distal loop, comprising residues Asp 68 to Ala 75, where motions on time scales up to milliseconds occur. Further, significant exchange contributions are observed for residues of the canonical binding site of SH3 domains including the RT-loop, the n-Src loop, for the loop comprising residues 13 to 19, which we refer to as the"disulfide loop", in part for the distal loop, and the carboxyl terminus of human MIA. The functional importance of this dynamic behavior is discussed with respect to the biological activity of several point mutations of human MIA. The results of this study suggest that the MIA protein and the recently identified highly homologous fibrocyte-derived protein (FDP)/MIA-like (MIAL) constitute a new family of secreted proteins that adopt an SH3 domain-like fold in solution with expanded ligand interactions. [source]

High-resolution structure of an ,-spectrin SH3-domain mutant with a redesigned hydrophobic core

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010
Ana Cámara-Artigas
The ,-spectrin SH3 domain (Spc-SH3) is a small modular domain which has been broadly used as a model protein in folding studies and these studies have sometimes been supported by structural information obtained from the coordinates of Spc-SH3 mutants. The structure of B5/D48G, a multiple mutant designed to improve the hydrophobic core and as a consequence the protein stability, has been solved at 1,Å resolution. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a = 24.79, b = 37.23, c = 62.95,Å. This mutant also bears a D48G substitution in the distal loop and this mutation has also been reported to increase the stability of the protein by itself. The structure of the B5/D48G mutant shows a highly packed hydrophobic core and a more ordered distal loop compared with previous Spc-SH3 structures. [source]