Atomic structures of two novel immunoglobulin-like domain pairs in the actin cross-linking protein filamin.

Filamins are actin filament cross-linking proteins composed of an N-terminal actin-binding domain and 24 immunoglobulin-like domains (IgFLNs). Filamins interact with numerous proteins, including the cytoplasmic domains of plasma membrane signaling and cell adhesion receptors. Thereby filamins mechanically and functionally link the cell membrane to the cytoskeleton. Most of the interactions have been mapped to the C-terminal IgFLNs 16-24. Similarly, as with the previously known compact domain pair of IgFLNa20-21, the two-domain fragments IgFLNa16-17 and IgFLNa18-19 were more compact in small angle x-ray scattering analysis than would be expected for two independent domains. Solution state NMR structures revealed that the domain packing in IgFLNa18-19 resembles the structure of IgFLNa20-21. In both domain pairs the integrin-binding site is masked, although the details of the domain-domain interaction are partly distinct. The structure of IgFLNa16-17 revealed a new domain packing mode where the adhesion receptor binding site of domain 17 is not masked. Sequence comparison suggests that similar packing of three tandem filamin domain pairs is present throughout the animal kingdom, and we propose that this packing is involved in the regulation of filamin interactions through a mechanosensor mechanism.

Metabolite phantom correction of the nonuniform volume-selection profiles in MR spectroscopic imaging: application to temporal lobe epilepsy.

BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.