title: Flexibility and rigidity, requirements for the function of proteins and protein pigment complexes. Eleventh Keilin memorial lecture.
abstract: Proteins may be rigid or flexible to various degrees as required for optimum function. Flexibility at the level of amino acid side-chains occurs universally and is important for binding and catalysis. Flexibility of large parts of a protein which rearrange or move are particularly interesting and will be discussed here. We differentiate between certain categories of large-scale flexibility although the boundaries between them are diffuse: flexibility of peptide segments, domain motions and order-disorder transitions of spatially contigous regions. The domains may be flexibly linked to allow rather unrestricted motion or the motion may be constrained to certain modes. The polypeptide segments linking the domains show characteristic structural features. The various categories of flexibility will be illustrated with the following examples. (a) Small protein proteinase inhibitors which are rather rigid molecules which provide binding surfaces complementary to their cognate proteases, but also show limited segmental flexibility and adaptation. (b) Large plasma inhibitors which exhibit large conformational changes upon interaction with proteases probably for regulatory purposes. (c) Pancreatic serine proteases which employ a disorder-order transition of their activation domain as a means to regulate enzymic activity. (d) Immunoglobulins in which rather unrestricted and also hinged domain motions occur in different parts of the molecule probably to allow binding to antigens in different arrangements. (e) Citrate synthase which adopts open and closed forms by a hinged domain motion to bind substrates and release products and to perform the catalytic condensation reaction, respectively. (f) The bifunctional multienzyme complex riboflavin synthase in which two enzymes (alpha and beta) catalyse two consecutive enzymic reactions. The beta-subunits form a shell, in which the alpha-subunits are enclosed. Diffusional motion of the catalytic intermediates is therefore restricted. In addition, segmental rearrangement occurs in the assembly of the beta-subunit. In contrast, rigidity is the dominant impression provided by the structures of the light harvesting complexes and the reaction centres involved the photosynthetic light reactions. These are large protein complexes in which the proteins serve as matrices to hold the pigments in the appropriate conformation and relative arrangement. Since motion would contribute to deactivation of the photo-excited states of the pigments and diminish the efficiency of light energy and electron transfer, a functional role for rigidity is easy to rationalize for these proteins.
mesh_terms: D002950:Citrate (si)-Synthase; D003460:Crystallization; D007074:Immunoglobulin G; D008958:Models, Molecular; D011480:Protease Inhibitors; D011487:Protein Conformation; D011506:Proteins; D012258:Riboflavin Synthase; D012697:Serine Endopeptidases; D013816:Thermodynamics; D014961:X-Ray Diffraction; D000515:alpha 1-Antitrypsin
chemical_list: D007074:Immunoglobulin G; D011480:Protease Inhibitors; D011506:Proteins; D000515:alpha 1-Antitrypsin; D002950:Citrate (si)-Synthase; D012258:Riboflavin Synthase; D012697:Serine Endopeptidases