Molecular details of ligand selectivity determinants in a promiscuous β-glucan periplasmic binding protein

BMC Structural Biology

Matthew J Cuneo¹  Dean A Myles¹  Xun Lu¹  Sudipa Ghimire-Rijal¹  Christopher B Stanley¹  Parthapratim Munshi² 

[1]Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA

[2]Department of Chemistry & Center for Informatics, Shiv Nadar University, Dadri, Uttar Pradesh 203207, India

关键词: Ligand specificity;    ABC transport;    Laminarin;    Carbohydrate recognition;    Periplasmic binding protein;   

Others  :  1091023
DOI  :  10.1186/1472-6807-13-18

 received in 2013-06-21, accepted in 2013-09-27,  发布年份 2013

【 摘 要 】

Background

Members of the periplasmic binding protein (PBP) superfamily utilize a highly conserved inter-domain ligand binding site that adapts to specifically bind a chemically diverse range of ligands. This paradigm of PBP ligand binding specificity was recently altered when the structure of the Thermotoga maritima cellobiose-binding protein (tmCBP) was solved. The tmCBP binding site is bipartite, comprising a canonical solvent-excluded region (subsite one), adjacent to a solvent-filled cavity (subsite two) where specific and semi-specific ligand recognition occur, respectively.

Results

A molecular level understanding of binding pocket adaptation mechanisms that simultaneously allow both ligand specificity at subsite one and promiscuity at subsite two has potentially important implications in ligand binding and drug design studies. We sought to investigate the determinants of ligand binding selectivity in tmCBP through biophysical characterization of tmCBP in the presence of varying β-glucan oligosaccharides. Crystal structures show that whilst the amino acids that comprise both the tmCBP subsite one and subsite two binding sites remain fixed in conformation regardless of which ligands are present, the rich hydrogen bonding potential of water molecules may facilitate the ordering and the plasticity of this unique PBP binding site.

Conclusions

The identification of the roles these water molecules play in ligand recognition suggests potential mechanisms that can be utilized to adapt a single ligand binding site to recognize multiple distinct ligands.

【 授权许可】

   
2013 Munshi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Neiditch MB, Federle MJ, Miller ST, Bassler BL, Hughson FM: Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2. Mol Cell 2005, 18(5):507-518.
• [2]Aksamit RR, Koshland DE Jr: Identification of the ribose binding protein as the receptor for ribose chemotaxis in Salmonella typhimurium. Biochemistry 1974, 13(22):4473-4478.
• [3]Iida A, Harayama S, Iino T, Hazelbauer GL: Molecular cloning and characterization of genes required for ribose transport and utilization in Escherichia coli K-12. J Bacteriol 1984, 158(2):674-682.
• [4]Shuman HA: Active transport of maltose in Escherichia coli K12. Role of the periplasmic maltose-binding protein and evidence for a substrate recognition site in the cytoplasmic membrane. J Biol Chem 1982, 257(10):5455-5461.
• [5]Kelly DJ, Thomas GH: The tripartite ATP-independent periplasmic (TRAP) transporters of bacteria and archaea. FEMS Microbiol Rev 2001, 25(4):405-424.
• [6]Campobasso N, Costello CA, Kinsland C, Begley TP, Ealick SE: Crystal structure of thiaminase-I from Bacillus thiaminolyticus at 2.0 A resolution. Biochemistry 1998, 37(45):15981-15989.
• [7]Friedman AM, Fischmann TO, Steitz TA: Crystal structure of lac repressor core tetramer and its implications for DNA looping. Science 1995, 268(5218):1721-1727.
• [8]Frandsen A, Pickering DS, Vestergaard B, Kasper C, Nielsen BB, Greenwood JR, Campiani G, Fattorusso C, Gajhede M, Schousboe A, et al.: Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2. Mol Pharmacol 2005, 67(3):703-713.
• [9]Bruns CM, Nowalk AJ, Arvai AS, McTigue MA, Vaughan KG, Mietzner TA, McRee DE: Structure of Haemophilus influenzae Fe(+3)-binding protein reveals convergent evolution within a superfamily. Nat Struct Biol 1997, 4(11):919-924.
• [10]Sun YJ, Rose J, Wang BC, Hsiao CD: The structure of glutamine-binding protein complexed with glutamine at 1.94 A resolution: comparisons with other amino acid binding proteins. J Mol Biol 1998, 278(1):219-229.
• [11]Berntsson RP, Thunnissen AM, Poolman B, Slotboom DJ: Importance of a hydrophobic pocket for peptide binding in lactococcal OppA. J Bacteriol 2011, 193(16):4254-4256.
• [12]Chaudhuri BN, Ko J, Park C, Jones TA, Mowbray SL: Structure of D-allose binding protein from Escherichia coli bound to D-allose at 1.8 A resolution. J Mol Biol 1999, 286(5):1519-1531.
• [13]Cuneo MJ, Beese LS, Hellinga HW: Structural analysis of semi-specific oligosaccharide recognition by a cellulose-binding protein of thermotoga maritima reveals adaptations for functional diversification of the oligopeptide periplasmic binding protein fold. J Biol Chem 2009, 284(48):33217-33223.
• [14]Sugiyama S, Vassylyev DG, Matsushima M, Kashiwagi K, Igarashi K, Morikawa K: Crystal structure of PotD, the primary receptor of the polyamine transport system in Escherichia coli. J Biol Chem 1996, 271(16):9519-9525.
• [15]Tirado-Lee L, Lee A, Rees DC, Pinkett HW: Classification of a Haemophilus influenzae ABC transporter HI1470/71 through its cognate molybdate periplasmic binding protein, MolA. Structure 2011, 19(11):1701-1710.
• [16]Mauchline TH, Fowler JE, East AK, Sartor AL, Zaheer R, Hosie AH, Poole PS, Finan TM: Mapping the Sinorhizobium meliloti 1021 solute-binding protein-dependent transportome. Proc Natl Acad Sci USA 2006, 103(47):17933-17938.
• [17]Cuneo MJ, Beese LS, Hellinga HW: Ligand-induced conformational changes in a thermophilic ribose-binding protein. BMC Struct Biol 2008, 8:50. BioMed Central Full Text
• [18]Magnusson U, Chaudhuri BN, Ko J, Park C, Jones TA, Mowbray SL: Hinge-bending motion of D-allose-binding protein from Escherichia coli: three open conformations. J Biol Chem 2002, 277(16):14077-14084.
• [19]Magnusson U, Salopek-Sondi B, Luck LA, Mowbray SL: X-ray structures of the leucine-binding protein illustrate conformational changes and the basis of ligand specificity. J Biol Chem 2004, 279(10):8747-8752.
• [20]Shilton BH, Flocco MM, Nilsson M, Mowbray SL: Conformational changes of three periplasmic receptors for bacterial chemotaxis and transport: the maltose-, glucose/galactose- and ribose-binding proteins. J Mol Biol 1996, 264(2):350-363.
• [21]Fukami-Kobayashi K, Tateno Y, Nishikawa K: Domain dislocation: a change of core structure in periplasmic binding proteins in their evolutionary history. J Mol Biol 1999, 286(1):279-290.
• [22]Berntsson RP, Smits SH, Schmitt L, Slotboom DJ, Poolman B: A structural classification of substrate-binding proteins. FEBS Lett 2010, 584(12):2606-2617.
• [23]Borrok MJ, Kiessling LL, Forest KT: Conformational changes of glucose/galactose-binding protein illuminated by open, unliganded, and ultra-high-resolution ligand-bound structures. Protein Sci 2007, 16(6):1032-1041.
• [24]Bagaria A, Kumaran D, Burley SK, Swaminathan S: Structural basis for a ribofuranosyl binding protein: insights into the furanose specific transport. Proteins 2011, 79(4):1352-1357.
• [25]Marvin JS, Hellinga HW: Manipulation of ligand binding affinity by exploitation of conformational coupling. Nat Struct Biol 2001, 8(9):795-798.
• [26]Toth-Petroczy A, Tawfik DS: Slow protein evolutionary rates are dictated by surface-core association. Proc Natl Acad Sci USA 2011, 108(27):11151-11156.
• [27]Dwyer MA, Hellinga HW: Periplasmic binding proteins: a versatile superfamily for protein engineering. Curr Opin Struct Biol 2004, 14(4):495-504.
• [28]Gould AD, Telmer PG, Shilton BH: Stimulation of the maltose transporter ATPase by unliganded maltose binding protein. Biochemistry 2009, 48(33):8051-8061.
• [29]Bjorkman AJ, Mowbray SL: Multiple open forms of ribose-binding protein trace the path of its conformational change. J Mol Biol 1998, 279(3):651-664.
• [30]Alicea I, Marvin JS, Miklos AE, Ellington AD, Looger LL, Schreiter ER: Structure of the Escherichia coli phosphonate binding protein PhnD and rationally optimized phosphonate biosensors. J Mol Biol 2011, 414(3):356-369.
• [31]Karpowich NK, Huang HH, Smith PC, Hunt JF: Crystal structures of the BtuF periplasmic-binding protein for vitamin B12 suggest a functionally important reduction in protein mobility upon ligand binding. J Biol Chem 2003, 278(10):8429-8434.
• [32]Nanavati DM, Thirangoon K, Noll KM: Several archaeal homologs of putative oligopeptide-binding proteins encoded by Thermotoga maritima bind sugars. Appl Environ Microbiol 2006, 72(2):1336-1345.
• [33]Zverlov VV, Volkov IY, Velikodvorskaya TV, Schwarz WH: Highly thermostable endo-1,3-beta-glucanase (laminarinase) LamA from Thermotoga neapolitana: nucleotide sequence of the gene and characterization of the recombinant gene product. Microbiology 1997, 143(Pt 5):1701-1708.
• [34]Conners SB, Montero CI, Comfort DA, Shockley KR, Johnson MR, Chhabra SR, Kelly RM: An expression-driven approach to the prediction of carbohydrate transport and utilization regulons in the hyperthermophilic bacterium Thermotoga maritima. J Bacteriol 2005, 187(21):7267-7282.
• [35]Cuneo MJ, Changela A, Beese LS, Hellinga HW: Structural adaptations that modulate monosaccharide, disaccharide, and trisaccharide specificities in periplasmic maltose-binding proteins. J Mol Biol 2009, 389(1):157-166.
• [36]Telmer PG, Shilton BH: Insights into the conformational equilibria of maltose-binding protein by analysis of high affinity mutants. J Biol Chem 2003, 278(36):34555-34567.
• [37]Cuneo MJ, Changela A, Miklos AE, Beese LS, Krueger JK, Hellinga HW: Structural analysis of a periplasmic binding protein in the tripartite ATP-independent transporter family reveals a tetrameric assembly that may have a role in ligand transport. J Biol Chem 2008, 283(47):32812-32820.
• [38]Gonin S, Arnoux P, Pierru B, Lavergne J, Alonso B, Sabaty M, Pignol D: Crystal structures of an Extracytoplasmic Solute Receptor from a TRAP transporter in its open and closed forms reveal a helix-swapped dimer requiring a cation for alpha-keto acid binding. BMC Struct Biol 2007, 7:11. BioMed Central Full Text
• [39]Wallace AC, Laskowski RA, Thornton JM: LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 1995, 8(2):127-134.
• [40]Millet O, Hudson RP, Kay LE: The energetic cost of domain reorientation in maltose-binding protein as studied by NMR and fluorescence spectroscopy. Proc Natl Acad Sci USA 2003, 100(22):12700-12705.
• [41]Cohen DS, Pielak GJ: Stability of yeast iso-1-ferricytochrome c as a function of pH and temperature. Protein Sci 1994, 3(8):1253-1260.
• [42]Zhao JK, Gao CY, Liu D: The extended Q-range small-angle neutron scattering diffractometer at the SNS. J Appl Cryst 2010, 43:1068-1077.
• [43]Wignall GD, Bates FS: Absolute calibration of small-angle neutron scattering data. J Appl Cryst 1987, 20:28-40.
• [44]Guinier A, Fournet G: Small-angle scattering of X-rays. New York: Wiley; 1955.
• [45]Svergun DI: Determination of the regularization parameter in indirect-transform methods using perceptual criteria. J Appl Cryst 1992, 25:495-503.
• [46]Svergun DI, Petoukhov MV, Koch MH: Determination of domain structure of proteins from X-ray solution scattering. Biophys J 2001, 80(6):2946-2953.
• [47]Otwinowski ZaM W: Processing of X-ray diffaction data collected in oscillation mode. Methods Enzymol 1997, 276A:307-326.
• [48]Collaborative Computational Project N: The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 1994, 50(Pt 5):760-763.
• [49]Emsley P, Cowtan K: Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 2004, 60(Pt 12 Pt 1):2126-2132.
• [50]Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, et al.: PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 2010, 66(Pt 2):213-221.
• [51]Davis IW, Murray LW, Richardson JS, Richardson DC: MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res 2004, 32:W615-619. Web Server issue
• [52]Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res 2000, 28(1):235-242.