Mutations can cause large changes in the conformation of a denatured protein

Deletion of 13 amino acids from the carboxyl terminus of staphylococcal nuclease (WTSNase delta) results in a denatured, partially unfolded molecule that lacks significant persistent secondary structure but is relatively compact and monomeric under physiological conditions [Shortle & Meeker (1989) Biochemistry 28, 936-944; Flanagan et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 748-752]. Because of these and other properties of the SNase delta polypeptide, it is a useful model system for investigating the conformation of the denatured state of a protein without using extreme temperature or solvent conditions. Moreover, since the modification is a carboxyl-terminal deletion, SNase delta may also resemble a transient state of the polypeptide chain as it emerges from a ribosome prior to its folding. In the present study, we have examined the sizes and conformations of mutated forms of SNase delta, using small-angle X-ray scattering and circular dichroism spectroscopy. Seven mutated forms were studied: four with single substitutions, two with double substitutions, and one triple substitution. When present in the full-length SNase, each of these mutated forms exhibited unusual behavior upon solvent or thermal denaturation. In the case of the truncated form (SNase delta), the small-angle scattering curves of the mutated forms fall into two classes: one resembling the scattering curve of compact native nuclease and the other having features consistent with those expected for an expanded coil-like polymer. In contrast, the scattering curve of WT SNase delta exhibits features intermediate between those observed for globular proteins and random polymers. The amino acid substitutions that gave rise to compact, native-like versions of SNase delta were all of the m--type (m-substitutions are predicted to decrease the size of the denatured state). Those which gave rise to versions of SNase delta that were more extended and coil-like than WT SNase delta were of the m+ type (m+ substitutions are predicted to increase the size of the denatured state). Estimates of the residual secondary structure present in WT SNase delta, as well as both the m+ and m-substituted versions of SNase delta, as determined by CD, suggest that the formation of secondary structure and compaction of the polypeptide chain occur concurrently. Our results show that single amino acid substitutions can radically alter the conformational distribution of a partially condensed polypeptide chain.(ABSTRACT TRUNCATED AT 400 WORDS)     

Is the Promissory Note of Personality as Vulnerability to Depression in Default? Reply to Zuroff, Mongrain, and Santor (2004).

In contrast to D. C. Zuroff, M. Mongrain, and D. A. Santor (2004), the current authors find the promissory note of dependency-sociotropy (DEP-SOC) and self-criticism-autonomy (SC-AUT) as a model of risk for depression to be in default. The authors propose reorganizing what has been cast as unitary effort into 3 distinct endeavors: a psychoanalytic clinical theory, development of a refined empirical model of risk for clinical depression, and research examining the effects of DEP-SOC and SC-AUT on interpersonal relationships in nonclinical samples. The authors identify some issues that need to be accommodated regardless of whether the assessment of Zuroff et al. (2004) or their own is accepted. DEP-SOC and SC-AUT are best construed as correlated, continuous dimensions. Future work also needs to accommodate depression as chronic recurrent condition, advances in developmental psychopathology, and more stringent criteria for positing a risk factor for clinical disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normative data for the Wechsler Memory Scale—Revised: 25- to 34-year olds.

The normative data provided in the Wechsler Memory Scale—Revised (WMS—R) manual for individuals aged 25–34 yrs were estimated statistically by interpolation. As an empirical check of this procedure, a representative stratified sample in this age range was selected to match the 1980 US Census data on relevant demographic characteristics. Prorated Full Scale IQs for the group were normally distributed, having a mean of 101.3 (SD?=?14.58, range?=?72–231). Differences between the empirically derived and published index scores appeared to be clinically significant. Substantial intra-individual differences were common when Visual–Verbal or General–Attention/Concentration indexes were compared. Normative data for the WMS—R subtests, indexes, and distribution of differences between indexes is provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Absorption spectra of solid rare earth complexes obtained from the inner filter effect on luminescence

The inner filter effect is observed in luminescence whenever a second substance is present that has absorptions which overlap the luminescence. This results in a diminution of the luminescence at those wavelengths and is generally observed in solution. In the present communication we show that this effect can be observed when a solid rare earth complex is physically mixed with a solid luminescent organic matrix with which it does not interact. The resulting luminescence is reduced in emission intensity at those wavelengths corresponding to the absorptions of the rare earth ion. This is illustrated with a mixture of Na₃[Ho(ODA)₃] ·2NaClO₄·6H₂O and pyrene at 77 K, and it is shown that the absorption spectrum of the holmium complex can be extracted from the luminescence spectrum of pyrene. This absorption spectrum is in good agreement with that obtained by conventional spectroscopy with a single crystal.