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Multistep Mechanism of Chloride Translocation in a Strongly Anion-Selective Porin Channel

Ulrich Zachariae ^*, Volkhard Helms  and Harald Engelhardt ^*

^* Max Planck Institute for Biochemistry, Martinsried, Germany; and Max Planck Institute for Biophysics, Frankfurt, Germany

Correspondence: Address reprint requests to Dr. Harald Engelhardt, Molekulare Strukturbiologie, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany. Tel.: 49-898-578-2650; Fax: 49-898-578-2641; E-mail: engelhar{at}biochem.mpg.de.

The strongly anion-selective porin channel Omp32 from the bacterium Delftia acidovorans differs from other unspecific porins by its pronounced selectivity for anions and its particularly small channel cross-section. Multinanosecond molecular dynamics simulations of chloride ion movement in this pore protein suggest that translocated anions interact intimately with the charges of a "basic ladder", whose dynamics lead the anions in a stepwise manner through the constriction zone of the channel. The ladder-steps comprise the central clustered arginine groups and flanking basic residues at its exoplasmic and periplasmic sides. The computed free energy profile of ion movement in and around the constriction zone shows a corresponding succession of free energy minima and barriers. A number of polar atoms from other amino acids contribute to the coordination of Cl^- at certain sites and to its temporary immobilization in the channel. A special binding site occurs at the transition of the constriction zone to the periplasmic funnel, binding the chloride ion over significant lengths of time. The results from our MD study offer a possible explanation for the nonlinear conductance properties and unusual salt-dependent characteristics of Omp32 observed earlier in experimental measurements.

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