Did evolution create a flexible ligand-binding cavity in the urokinase receptor through deletion of a plesiotypic disulfide bond?

The urokinase receptor (uPAR) is a founding member of a small protein family with multiple Ly6/uPAR (LU) domains. The motif defining these LU domains contains five plesiotypic disulfide bonds stabilizing its prototypical three-fingered fold having three protruding loops. Notwithstanding the detailed knowledge on structure-function relationships in uPAR, one puzzling enigma remains unexplored. Why does the first LU domain in uPAR (DI) lack one of its consensus disulfide bonds, when the absence of this particular disulfide bond impairs the correct folding of other single LU domain-containing proteins? Here, using a variety of contemporary biophysical methods, we found that reintroducing the two missing half-cystines in uPAR DI caused the spontaneous formation of the corresponding consensus 7–8 LU domain disulfide bond. Importantly, constraints due to this cross-link impaired (i) the binding of uPAR to its primary ligand urokinase and (ii) the flexible interdomain assembly of the three LU domains in uPAR. We conclude that the evolutionary deletion of this particular disulfide bond in uPAR DI may have enabled the assembly of a high-affinity urokinase-binding cavity involving all three LU domains in uPAR. Of note, an analogous neofunctionalization occurred in snake venom α-neurotoxins upon loss of another pair of the plesiotypic LU domain half-cystines. In summary, elimination of the 7–8 consensus disulfide bond in the first LU domain of uPAR did have significant functional and structural consequences

Interplay of nonlinearity and geometry in a DNA-related, Klein-Gordon model with long-range dipole-dipole interaction

Most of the studies on mathematical models of DNA are limited to next neighbor interaction. However, the coupling between base pairs is thought to be caused by dipole interaction, and, when the DNA strand is bent, the distances between base pairs become shorter, therefore the interactions with distant base pairs have to be taken into account. In this paper we analyze the existence and stability of breathers, i.e., localized oscillations in a simple model of bent DNA with long-range dipole interaction. Breathers have been suggested as precursors of the denaturation bubble

Strong-field approximation for Coulomb explosion of H_2^+ by short intense laser pulses

We present a simple quantum mechanical model to describe Coulomb explosion of H$_2^+$ by short, intense, infrared laser pulses. The model is based on the length gauge version of the molecular strong-field approximation and is valid for pulses shorter than 50 fs where the process of dissociation prior to ionization is negligible. The results are compared with recent experimental results for the proton energy spectrum [I. Ben-Itzhak et al., Phys. Rev. Lett. 95, 073002 (2005), B. D. Esry et al., Phys. Rev. Lett. 97, 013003 (2006)]. The predictions of the model reproduce the profile of the spectrum although the peak energy is slightly lower than the observations. For comparison, we also present results obtained by two different tunneling models for this process.Comment: 8 pages, 4 figure