Mercury binding protein

from Shigella flexneri

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Because of their affinity to sulfhydryl groups mercury ions are toxic for living cells. One possibility of detoxification is the reduction to the uncharged metal which may be eliminated from the cell more easily because of its volatility. To accomplish this Gram-negative bacteria harbour in their cytoplasm the reductase MerA. Hg²⁺-ions that happened to get into the periplasm are transported into the cytoplasm by MerTC with the aid of the binding protein MerP in the periplasm. Functional MerP consists of 72 amino acids after cleaving off of 18 amino acids signal sequence.

Structural components of MerP are a four stranded antiparallel beta sheet and two alpha helices in contact with the sheet (alpha-beta sandwich) . The loop between beta strand 1 and helix 1 holds the sequence characteristic for heavy metal binding proteins, GMTCxxC . The metal ions are bound by the SH-groups of the cystein residues . The result of the binding is a conformational change of the protein : in the conformation free of mercury Cys17 is part of helix 1 , after binding to the heavy metal Cys17 cannot form hydrogen bonds to the helix . By binding the Hg²⁺ the distance of the sulphur atoms of the cysteines is deminished from 10 Å to 4,65 Å.

In the adjacing loops there are also positional shifts for some amino acids, especially Phe38 and Glu39 : the negative charge of the glutamic acid compensates for the charge of the mercury ion, the phenylalanine residue increases the hydrophobicity . Thus free and bound form of the protein exhibit different surface properties for recognition by the transport system MerTC.

Literature:
RA Steele & SJ Opella, Structures of the reduced and mercury-bound forms of MerP, the periplasmic protein from the bacterial mercury detoxification system, Biochemistry 36 (1997) 6885-6895
H Qian et al, NMR solution structure of the oxidized form of MerP, a mercuric ion binding protein involved in bacterial mercuric ion resistance, Biochemistry 37 (1998) 9316-9322

6-99 - R Bergmann