Motion in Lac Repressor (Overall motion) [lacr]

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Classification Complex Motion [C----]

Description This protein has two possible motions: (1) The LacR core is a dimer of dimers. The monomer in each dimer, in turn, contains two domains (the core domains) that are similar to the bacterial periplasmic binding proteins, such as the ribose binding proteins, and to the purine repressor (PurR). Like the periplasmic binding proteins, these undergo a hinged domain closure (involving 3 hinges) when the a molecule binds in the cleft between them (the inducer molecule ITPG). This motion involves one domain (the N-terminal core domain) opening up through a 10 degree rotation and a 2 A translation. The maximum displacements are up to 3.5 A. The more open form has the inducer bound. In this state the two core domains change their positioning relative to two other domains (the DNA binding headpiece and the tetrametrization domain). This is the root of the allosteric control. It changes the DNA binding affinity of the head-piece and perhaps enables the two dimers in the tetramer to move to different relative dispositions. When the two core domains change their disposition, it involves breaking salt bridges over a dimer interface and each monomer in a dimer separating by up to 3 A. Each monomer of these proteins is expected to undergo a similar motion, but smaller motion, upon binding inducer. This is expected to affect the relative positioning of the DNA binding domains. (2) The two dimers in the tetramer are held together by a small dimerization domain. It is expected that the structure of this small domain is somewhat flexible and can accomodate a range of motion of the two LacR core dimers. This, in turn, allows the protein to bind DNA sequences with a variety of spacings between operators. This motion will involve the a single polypeptide chain in each monomer connected to the tetrametization domain.

Particular values describing motion = 340-357 (tetramerization domain helix) = 6-45 (HTH domain) Domain 1 (residue selection) = 63-161,294-318 (N-term. domain of Core) Domain 2 (residue selection) = 164-290,322-324 (C-term. domain of Core) Location of a Hinge (residue selection) = 162-163 (core region hinge 1) Location of a Hinge (residue selection) = 291-293 (core region hinge 2) Location of a Hinge (residue selection) = 319-321 (core region hinge 3) Location of a Hinge (residue selection) = 325-339 (flex. linker to tet. domain) Location of a Hinge (residue selection) = 46-62 (linker region) Experimental Methods = xn (Traditional X-ray and NMR) Creation Date = 19970822 Modification Date = 19970822

References Lewis M; Chang G; Horton NC; Kercher MA; Pace HC; Schumacher MA; Brennan RG; Lu P. Crystal structure of the lactose operon repressor and its complexes with DNA and inducer [see comments]. Science, 1996 Mar 1, 271(5253):1247-54. [Medline info for 96239623]

Data and Graphics Graphic-1 With Inducer Graphic-2 Without Inducer Graphic-3 Bound to DNA

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Copyright 1995-2005 M. Gerstein, W. Krebs, S. Flores, N. Echols, and others
Email: Mark.Gerstein _at_ yale.edu