Table 1: Proteins that Undergo Domain Movements (A) Proteins for which open and closed conformations are known a b (i) Domain motion is predominantly shear Citrate Synthase c 1CTS 3CTS Remington et al., 1982; Lesk & Chothia, 1984 Shear motions at many helix-helix interfaces shift mainchain atoms up to 10 Aspartate Amino Transferase (AAT) c 9AAT 1AMA McPhalen et al., 1992 Shear motion at 2 interfaces combined with hinge in a kinked helix. Trp Repressor c 1WRP 2WRP 3WRP Lawson et al.,1988 Shear motion between 2 helices adjusts position of helix-turn-helix reading head domain to enable it to bind DNA Hexokinase c 2YHX 1HKG Bennett & Steitz, 1978, 1980; Lesk & Chothia, 1984 Shear motion with XBAaba layering. Prominent crossed helices at interdomain interface. Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) c 1GD1 2GD1 Skarzynski & Wonacott, 1988 Shear motion with XBAaba layering. Alcohol Dehydrogenase (ADH) c 8ADH 6ADH Eklund et al.,1981; Colonna-Cesari et al., 1986 Shear motion with XBAaba layering and 2 hinges. Endothiapepsin 4APE 5ER2 Sali et al., 1989; 1992 Small shearing motion at 1 interface between domains (17¡ rotation and 1 displacement) (ii) Domain motion is predominantly hinge Tomato Bushy Stunt Virus (TBSV) Coat Protein c e 2TBV Olson et al., 1983 1 interdomain linkage,1 hinge, ~22¡ rotation. Lactoferrin c 1LFH 1LFG Anderson et al., 1990; Gerstein et al., 1993b 2 interdomain linkages, 2 hinges (in a b-sheet), 53¡ rotation. See-saw between two interfaces. Maltodextrin Binding Protein (MBP) c 1OMF 2MBP Sharff et al., 1992; 3 interdomain linkages, 3 hinges, 35¡ rotation. Lysine/Arginine/Ornithine (LAO) binding protein c 1LST Oh et al., 1993 2 interdomain linkages, 2 hinges, 52¡ rotation. T4 lysozyme mutants: Ile3®Pro & Met6®Ile c 1L96 1L97 Dixon et al., 1992; Faber & Matthews, 1991 2 hinges, at either end of interdomain helix, produce rotations up to 32¡. Adenylate Kinase (ADK) c g 1AK3 1AKE Schulz et al., 1990; Gerstein et al., 1993a 2 interdomain linkages and 4 hinges (one involves kinking helix). 60¡ rotation from 1st pair of hinges, 30¡ from 2nd pair, 90¡ total. Catabolite Gene Activator Protein (CAP) e 3GAP Weber & Steitz, 1987 1 interdomain linkage and 1 hinge. Comparison of subunits in the dimer reveals that the small domain has rotated ~30¡ closer to the large domain in one subunit. cAMP-dependent Protein Kinase (catalytic domain) c d 1ATP 1APM Karlsson et al., 1993 1st set of hinges, involving 3 interdomain linkages, produces 12¡ rotation of domain cores (with ~3 shift). 2nd set of hinges produces further 6¡ rotation of a loop. 1 shearing interface between domains. Calmodulin c 1CLL 4CLL 2BBM Ikura et al., 1992; Meador et al., 1992, 1993 1 interdomain linkage, 1 hinge, ~150¡ rotation. Hinge involves long helix splitting into 2 helices (inclined at ~100¡) with strand in between. Glutamate Dehydrogenase Stillman et al., 1993 13¡ rotation of 1 domain relative to other (iii) Domain motion is not predominantly a hinge or shear mechanism Immunoglobulins c h 2FB4 1MCP Bennett & Huber, 1984; Lesk & Chothia, 1988; Hinge motion in linking peptides. Ball & socket joint forms interface between domains. Range of rotations up to 50¡ allowed. Serpins 5API 1OVA Loebermann et al., 1984 Engh et al., 1990 Stein & Chothia, 1991 Mottonen et al., 1992 Translation at a helix-sheet interface results in the transformation of the tertiary structure by insertion of strand into sheet. (iv) Domain motion can not be fully classified at present f HI V-1 Reverse Transcriptase 1HMI 1HVT Kohlstaedt et al., 1992; Jacobo-Molina et al., 1993 Comparison of subunits shows very large rearrangement of 2 of the 4 domains which is accomodated by changes in loops and by unfolding of small 3 stranded b-sheet. TATA-box Binding Protein (TBP) e 1TBP Kim et al., 1993a, 1993b; Chasman et al., 1993 Twisting of a central sheet moves 2 domains ~10¡. Themolysin, Elastase, neutral proteases 1EZM 4TMN Holland et al., 1992; Thayer et al., 1991 Bending interdomain helix Elongation Factor Tu (EF-Tu) d 1ETU Berchtold et al., 1993; Kjeldgaard et al., 1993 Internal loop movements similar to those in ras protein (below) lead to large domain rearragements (90¡ rotation, 40 shifts) (B) Proteins for which only one conformation is known (i) Domain motion is predominantly shear Phosphoglycerate Kinase (PGK) c 3PGK Harlos et al., 1992 Similar to hexokinase (XBAabx layering) Heat Shock Protein 1HSC Flaherty et al. ,1990 Similar to hexokinase (XBAabx layering) Actin 1ATN Kabsch et al. ,1990; Flaherty et al., 1991 i Similar to hexokinase (XBAabx layering) Aspartic Proteases, besides endothiapepsin: Penicllopepsin, Rhizopuspepsin, Chymosin, Porcine Pepsin 2APP 2APR 2PEP 3CMS 1PSG Sali et al., 1992 Similar to endothiapepsin (ii) Domain motion is predominantly hinge Sulfate & Phosphate Binding Proteins 1SBP 1ABH Luecke & Quiocho, 1990; Pflugrath & Quiocho, 1988 Similar to MBP & lactoferrin. These are group-II periplasmic binding proteins. Arabinose, Leucine, & Galactose Binding Proteins 2LBP 2GBP 1ABP Gilliland & Quiocho, 1981; Vyas et al., 1988, 1991; Sack et al., 1989a,b Similar to MBP & lactoferrin. However, these are group-I periplasmic binding proteins and are not as similar as group-II ones (above) are. Transferrins (N-terminal lobe) 1TFD Sarra et al., 1990 Similar to lactoferrin Guanylate Kinase (GDK) 1GKY Stehle & Schulz, 1990 Similar to ADK Porphobilinogen Deaminase 1PDA Louie et al., 1992 Domains 1 and 2 similar to lactoferrin (iii) Domain motion can not be classified at present f Myosin Rayment et al., 1993 Closure of a nucleotide-binding cleft, with similarities to that of ADK, hypothesized to produce movements > 50 Transducin-a Noel et al., 1993 Similar movements to EF-Tu and ras expected (C) Proteins known in two conformations which involve movements of fragments smaller than domains a (i) Motion is predominantly shear Insulin d 4INS Chothia et al., 1983 Helices shear by ~1.5 . Thymidylate Synthase 3TMS 2TSC Perry et al., 1990; Montfort et al., 1990 Small shear motion of helices packed onto central sheet. Dihydrofolate Reductase (DHFR) 4DFR 5DFR Bystroff et al., 1991 Small (~3 ) movement, shearing interface with hinges. (ii) Motion is predominantly hinge Annexin V 1AVR 1RAN Sopkova et al., 1993; Concha, et al., 1993 Large movements of 2 loops and end of a helix moves a buried trp residue 18 to surface. Lactate Dehydrogenase (LDH) 6LDH 1LDM White et al., 1976; Gerstein & Chothia, 1991 Loop closure with 2 hinges, one in helix, moves Ca atoms ~11 Triose Phosphate Isomerase (TIM) 2YPI 3TIM 6TIM Lolis & Petsko, 1990; Joseph et al., 1990; Wirenga et al., 1991 Loop closure with 2 hinges moves Ca atoms ~ 7 Enolase 3ENL 7ENL Lebioda & Stec, 1991 Loop movements of ~7 HIV-1 protease 4HVP 3HVP 5HVP Miller et al., 1989; Fitzgerald et al., 1990 Two large loop regions, that together comprise one quarter of the structure, move Ca atoms ~ 7 Foot and mouth disease virus d 1BBT Parry et al., 1990 Comparing variants of virus shows movement of a surface loop Triglyceride Lipase 1TGL 4TGL Derewenda et al., 1992; 2 hinges on either side of a helix move Ca atoms up to12 . In one hinge a residue changes from an extended to a helical conformation. Isocitrate Dehydrogenase d 3ICD Stoddard & Koshland, 1993 Loop movements of ~2 Malate Dehydrogenase (MDH) e 4MDH Birktoft et al., 1989 Comparison of subunits shows a loop closure similar to LDH, moving atom Ca atoms up to 8 . ras Protein 4Q21 6Q21 Milburn et al., 1990; Sclichting et al., 1990 2 loop movements move Ca atoms up to 10 (one movement includes helix attached to loop). a When both open and closed forms are known, we refer to the papers that describe the structure comparisons. Further references to the individual open and closed structures can be found in these papers. b Allosteric proteins are not included because these proteins have motions that involve extensive repacking of interfaces (see Perutz, 1989 for a review). Such repacking involves high-energy conformational transitions distinctly different from the hinge and shear mechanisms. c Indicates proteins discussed in detail in the text. d Structures of 2 conformations have been solved but only 1 has been deposited in the Protein Data Bank. e Motion is evident in comparing different subunits in the asymmetric unit. Single data bank identifier applies for both forms. f It is not possible to classify some domain motions at present because full sets of coordinates or detailed analyses are not yet available. g ADK also has a shear motion when the first substrate, AMP, binds: i.e. in moving from the conformation of 3ADK to 1AK3, 3 helices with a crossed geometry shift 1-2 to rearrange the geometry of the nucleotide binding site slightly (Diederichs & Schulz, 1991). h Data bank indentifiers for only two of the many representative immunoglobulin stuctures are indicated. i This paper describes the structural similarity of actin and the heat-shock protein.