CFTR is a monomer: Biochemical and functional evidence

被引:30
作者
Chen, JH [1 ]
Chang, XB [1 ]
Aleksandrov, AA [1 ]
Riordan, JR [1 ]
机构
[1] Mayo Clin & Mayo Fdn, SC Johnson Med Res Ctr, Scottsdale, AZ 85259 USA
关键词
ABC protein; CFTR; chloride channel; cystic fibrosis; quaternary structure; CFTR monomer;
D O I
10.1007/s00232-001-0174-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although the CFTR protein alone is sufficient to generate a regulated chloride channel, it is unknown how many of the polypeptides form the channel. Using biochemical and functional assays, we demonstrate that the CFTR polypeptide is a monomer. CFTR sediments as a monomer in a linear, continuous sucrose gradient. Cells co-expressing different epitope-tagged CFTR provide no evidence of co-assembly in immunoprecipitation and nickel affinity binding experiments. Co-expressed wild-type and DeltaF508 CFTR are without influence on each other in their ability to progress through the secretory pathway, suggesting they do not associate in the endoplasmic reticulum. No hybrid conducting single channels are seen in planar lipid bilayers with which membrane vesicles from cells co-expressing similar amounts of two different CFTR conduction species have been fused.
引用
收藏
页码:55 / 71
页数:17
相关论文
共 86 条
  • [1] Toward understanding the assembly and structure of KATP channels
    Aguilar-Bryan, L
    Clement, JP
    Gonzalez, G
    Kunjilwar, K
    Babenko, A
    Bryan, J
    [J]. PHYSIOLOGICAL REVIEWS, 1998, 78 (01) : 227 - 245
  • [2] Regulation of CFTR ion channel gating by MgATP
    Aleksandrov, AA
    Riordan, JR
    [J]. FEBS LETTERS, 1998, 431 (01): : 97 - 101
  • [3] ALTERED PLASMA-MEMBRANE ULTRASTRUCTURE IN MULTIDRUG-RESISTANT CELLS
    ARSENAULT, AL
    LING, V
    KARTNER, N
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1988, 938 (02) : 315 - 321
  • [4] PURIFICATION AND FUNCTIONAL RECONSTITUTION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR)
    BEAR, CE
    LI, CH
    KARTNER, N
    BRIDGES, RJ
    JENSEN, TJ
    RAMJEESINGH, M
    RIORDAN, JR
    [J]. CELL, 1992, 68 (04) : 809 - 818
  • [5] DIMERIZATION OF THE P-GLYCOPROTEIN IN MEMBRANES
    BOSCOBOINIK, D
    DEBANNE, MT
    STAFFORD, AR
    JUNG, CY
    GUPTA, RS
    EPAND, RM
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1027 (03) : 225 - 228
  • [6] From ionic currents to molecular mechanisms: The structure and function of voltage-gated sodium channels
    Catterall, WA
    [J]. NEURON, 2000, 26 (01) : 13 - 25
  • [7] STRUCTURE AND FUNCTION OF VOLTAGE-SENSITIVE ION CHANNELS
    CATTERALL, WA
    [J]. SCIENCE, 1988, 242 (4875) : 50 - 61
  • [8] Severed molecules functionally define the boundaries of the cystic fibrosis transmembrane conductance regulator's NH2-terminal nucleotide binding domain
    Chan, KM
    Csanády, L
    Seto-Young, D
    Nairn, AC
    Gadsby, DC
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 2000, 116 (02) : 163 - 180
  • [9] RETRACTED: Structure of MsbA from E-coli:: A homolog of the multidrug resistance ATP binding cassette (ABC) transporters (Retracted Article. See vol 314, pg 1875, 2006)
    Chang, G
    Roth, CB
    [J]. SCIENCE, 2001, 293 (5536) : 1793 - 1800
  • [10] Structure of the MscL homolog from Mycobacterium tuberculosis:: A gated mechanosensitive ion channel
    Chang, G
    Spencer, RH
    Lee, AT
    Barclay, MT
    Rees, DC
    [J]. SCIENCE, 1998, 282 (5397) : 2220 - 2226