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Wuhan University Journal of Natural Sciences

, Volume 12, Issue 6, pp 1029–1033 | Cite as

Effect of residue mutation on the electrostatic potential in EcCIC

  • Zou Xianwu 
  • Dong Shuxiang 
  • Wang Xiaoqing 
  • Huang Shengyou 
Article
  • 75 Downloads

Abstract

The effect of mutation of strongly conserved porelining residues in the chloride channel EcClC on the electrostatic potential and binding free energy of the chloride ion was studied using explicit protein-membrane structures. Electrostatic potential distribution and binding free energy of the chloride ion at different binding sites in the wild-type and mutated EcClC were calculated with APBS. The potential data reveal that the electrostatic potential around the selectivity filter, especially around the site S ext and S cen becomes more negative as the residue R147 was mutated to C147. The electrostatic binding free energy shows that the binding free energy of the chloride ion at all binding sites becomes more positive as R147 was mutated. It follows that mutation of R147 decreases ion stabilization at binding sites and affects channel’s gating.

Key words

chloride channel electrostatic potential binding free energy mutation 

CLC number

O 469 Q 615 

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References

  1. [1]
    Jentsch T J, Friedrich T, Yamada H. Clc Chloride Channel Family[J]. Pflugers Arch, 1999, 437:783–795.CrossRefGoogle Scholar
  2. [2]
    Jentsch T J, Stein V, Weinreich F, et al. Molecular Structure and Physiological Function of Chloride Channels[J]. Phys Rev B, 2002, 82: 503–568.Google Scholar
  3. [3]
    Dutzler R, Campbell E B, Cadene M, et al. X-Ray Structure of a ClC Chloride Channel at 3.0 Angstrom Reveals the Molecular Basis of Anion Selectivity[J]. Nature, 2002, 415: 287–294.CrossRefGoogle Scholar
  4. [4]
    Faraldo-Gomez J D, Roux B. Electrostatics of Ion Stabilization in a ClC Chloride Channel Homologue from Escherichia Coli[J]. J Mol Biol, 2004, 339:981–1000.CrossRefGoogle Scholar
  5. [5]
    Cohen J, Schulten K. Mechanism of Anionic Conduction Across ClC[J]. Biophys J, 2004, 86:836–845.Google Scholar
  6. [6]
    Miloshevsky G V, Jordan P C. Anion Pathway and Potential Energy Profiles along Curvilinear Bacterial ClC Cl Pores: Electrostatic Effects of Charged Residues[J]. Biophys J, 2004, 86:825–835.Google Scholar
  7. [7]
    Corry B O, Mara M, Chung S H. Conduction Mechanisms of Chloride Ions in ClC-Type Channels[J]. Biophys J, 2004, 86:846–860.CrossRefGoogle Scholar
  8. [8]
    Lin C W, Chen T Y. Cysteine Modification of a Mutative Pore Residue in ClC-0 Implication for the Pore Stoichiometry of ClC Chloride Channels[J]. J Gen Physiol, 2000, 116:535–546.CrossRefGoogle Scholar
  9. [9]
    Humphrey W, Dalke A, Schulten K. VMD: Visual Molecular Dynamics[J]. J Mol Graph, 1996, 14(1):33–38.CrossRefGoogle Scholar
  10. [10]
    Kalé X, Skeel R, Schulten K. NAMD2:Greater Scalability for Parallel Molecular Dynamics[J]. Journal of Computational Physics, 1999, 151:283–312.zbMATHCrossRefGoogle Scholar
  11. [11]
    Baker N A, Sept D, Joseph S, et al. Electrostatics of Nanosystems: Application to Microtubules and the Ribosome [J]. Proc Natl Acad Sci, 2001, 98:10037–10041.CrossRefGoogle Scholar
  12. [12]
    MacKerell A D, Bashford D, Bellott M, et al. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins[J]. J Phys Chem B, 1998, 102:3586–3616.CrossRefGoogle Scholar
  13. [13]
    Smart O S, Goodfellow J M, Wallace B A. The Pore Dimensions of Gramicidin A[J]. Biophys J, 1993, 65:2455–2460.Google Scholar
  14. [14]
    Dutzler R, Campbell E B, MacKinnon R. Gating the Selectivity Filter in ClC Chloride Channels[J]. Science, 2003, 300:108–112.CrossRefGoogle Scholar
  15. [15]
    Lobet S, Dutzler R. Ion-Binding Properties of the ClC Chloride Selectivity Filter[J]. The EMBO Journal, 2006, 25:24–33.CrossRefGoogle Scholar

Copyright information

© Wuhan University 2007

Authors and Affiliations

  • Zou Xianwu 
    • 1
  • Dong Shuxiang 
    • 1
  • Wang Xiaoqing 
    • 1
  • Huang Shengyou 
    • 1
  1. 1.School of Physics and TechnologyWuhan UniversityWuhanChina

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