Unliganded GroEL at 2.8 A: structure and functional implications.

The three-dimensional structure of the E. coli chaperonin, GroEL, has been determined crystallographically and refined to 2.7 A in two crystal forms: an orthorhombic form from high salt and a monoclinic form from polyethylene glycol. The former is ligand free, the latter is both liganded with ATP analogues and ligand free. These structures provide a structural scaffold upon which to interpret extensive mutagenesis and biochemical studies. GroEL contains two sevenfold rotationally symmetric rings of identical 547-amino acid subunits. The rings are arranged 'back-to-back' with exact dyad symmetry to form a stubby cylinder that is 146 A high with an outer diameter of about 143 A. The cylinder has a substantial central channel that is unobstructed for the entire length of the cylinder and has a diameter of about 45 A except for large bulges that lead into a sevenfold symmetric array of elliptical side windows in each ring. Each subunit is composed of three distinct domains: (i) an 'equatorial' domain that contains the N- and C-terminus and the ATP-binding pocket, (ii) an 'apical domain' that forms the opening of the central channel and contains poorly ordered segments that mutational studies implicate in binding unfolded polypeptides and GroES, and (iii) an intermediate domain tht connects the other two domains and may serve to transmit allosteric adjustments.

[1]  C. Dobson,et al.  Conformation of GroEL-bound α-lactalbumin probed by mass spectrometry , 1994, Nature.

[2]  H. Saibil.  How chaperones tell wrong from right , 1994, Nature Structural Biology.

[3]  Neil A. Ranson,et al.  Location of a folding protein and shape changes in GroEL–GroES complexes imaged by cryo-electron microscopy , 1994, Nature.

[4]  Yechezkel Kashi,et al.  GroEL-mediated protein folding proceeds by multiple rounds of binding and release of nonnative forms , 1994, Cell.

[5]  G. Lorimer,et al.  Dynamics of the chaperonin ATPase cycle: implications for facilitated protein folding. , 1994, Science.

[6]  K. Kuwajima,et al.  The chaperonin GroEL does not recognize apo-α-lactalbumin in the molten globule state , 1994, Nature Structural Biology.

[7]  T. Creighton,et al.  Conformational specificity of the chaperonin GroEL for the compact folding intermediates of alpha‐lactalbumin. , 1994, The EMBO journal.

[8]  K. Wüthrich,et al.  Destabilization of the complete protein secondary structure on binding to the chaperone GroEL , 1994, Nature.

[9]  T. Langer,et al.  The reaction cycle of GroEL and GroES in chaperonin-assisted protein folding , 1993, Nature.

[10]  S. Chen,et al.  ATP induces large quaternary rearrangements in a cage-like chaperonin structure , 1993, Current Biology.

[11]  K. Braig,et al.  A polypeptide bound by the chaperonin groEL is localized within a central cavity. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[12]  K. Willison,et al.  Protein folding in the cell: functions of two families of molecular chaperone, hsp 60 and TF55-TCP1. , 1993 .

[13]  W. Baumeister,et al.  Chaperonin‐mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. , 1992, The EMBO journal.

[14]  J. Sambrook,et al.  Protein folding in the cell , 1992, Nature.

[15]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[16]  F. Hartl,et al.  Molecular chaperone functions of heat-shock proteins. , 1993, Annual review of biochemistry.