M. B. Abbott, V. Gaponenko, E. Abusamhadneh, N. Finley, G. Li et al., Regulatory Domain Conformational Exchange and Linker Region Flexibility in Cardiac Troponin C Bound to Cardiac Troponin I, Journal of Biological Chemistry, vol.275, issue.27, pp.20610-20617, 2000.
DOI : 10.1074/jbc.M909252199

A. A. Adzhubei and M. J. Sternberg, Conservation of polyproline II helices in homologous proteins: Implications for structure prediction by model building, Protein Science, vol.76, issue.12, pp.2395-2410, 1994.
DOI : 10.1002/pro.5560031223

F. H. Allen and O. Johnson, Automated conformational analysis from crystallographic data. 4. Statistical descriptors for a distribution of torsion angles, Acta Crystallographica Section B Structural Science, vol.47, issue.1, pp.62-67, 1991.
DOI : 10.1107/S0108768190010382

D. Altschuh, D. C. Tessier, and T. Vernet, Modulation of the enzymatic activity of papain by interdomain residues remote from the active site, "Protein Engineering, Design and Selection", vol.7, issue.6, pp.769-775, 1994.
DOI : 10.1093/protein/7.6.769

S. F. Altschul, T. L. Madden, A. A. Schaffer, J. Zhang, Z. Zhang et al., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Research, vol.25, issue.17, pp.3389-3402, 1997.
DOI : 10.1093/nar/25.17.3389

R. Arai, H. Ueda, A. Kitayama, N. Kamiya, and T. Nagamune, Design of the linkers which effectively separate domains of a bifunctional fusion protein, Protein Engineering Design and Selection, vol.14, issue.8, pp.529-532, 2001.
DOI : 10.1093/protein/14.8.529

L. Aravind and C. P. Ponting, The cytoplasmic helical linker domain of receptor histidine kinase and methyl-accepting proteins is common to many prokaryotic signalling proteins, FEMS Microbiology Letters, vol.176, issue.1, pp.111-116, 1999.
DOI : 10.1111/j.1574-6968.1999.tb13650.x

M. Bashton and C. Chothia, The geometry of domain combination in proteins, Journal of Molecular Biology, vol.315, issue.4, pp.927-939, 2002.
DOI : 10.1006/jmbi.2001.5288

M. J. Bennett, S. Choe, and D. Eisenberg, Domain swapping: entangling alliances between proteins., Proceedings of the National Academy of Sciences USA, pp.91-3127, 1994.
DOI : 10.1073/pnas.91.8.3127

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43528

M. J. Bennett and D. Eisenberg, Refined structure of monomelic diphtheria toxin at 2.3 ?? resolution, Protein Science, vol.263, issue.9, pp.1464-1475, 1994.
DOI : 10.1002/pro.5560030912

C. Benros, A. G. De-brevern, and S. Hazout, Analyzing the sequence???structure relationship of a library of local structural prototypes, Journal of Theoretical Biology, vol.256, issue.2, pp.215-226, 2009.
DOI : 10.1016/j.jtbi.2008.08.032

URL : https://hal.archives-ouvertes.fr/inserm-00318954

I. N. Berezovsky, Discrete structure of van der Waals domains in globular proteins, Protein Engineering Design and Selection, vol.16, issue.3, pp.161-167, 2003.
DOI : 10.1093/proeng/gzg026

I. N. Berezovsky, N. G. Esipova, and V. G. Tumanyan, Hierarchy of Regions of Amino Acid Sequence with Respect to Their Role in the Protein Spatial Structure, Journal of Computational Biology, vol.7, issue.1-2, pp.183-192, 2000.
DOI : 10.1089/10665270050081450

I. N. Berezovsky, A. Y. Grosberg, and E. N. Trifonov, Closed loops of nearly standard size: common basic element of protein structure, FEBS Letters, vol.23, issue.2-3, pp.283-286, 2000.
DOI : 10.1016/S0014-5793(00)01091-7

I. N. Berezovsky, V. M. Kirzhner, A. Kirzhner, V. R. Rosenfeld, and E. N. Trifonov, Closed loops: persistence of the protein chain returns, Protein Engineering Design and Selection, vol.15, issue.12, pp.955-957, 2002.
DOI : 10.1093/protein/15.12.955

I. N. Berezovsky, V. A. Namiot, V. G. Tumanyan, and N. G. Esipova, Hierarchy of the Interaction Energy Distribution in the Spatial Structure of Globular Proteins and the Problem of Domain Definition, Journal of Biomolecular Structure and Dynamics, vol.7, issue.1, pp.133-155, 1999.
DOI : 10.1103/PhysRev.73.360

I. N. Berezovsky and E. N. Trifonov, Van der Waals locks: Loop-n-lock structure of globular proteins11Edited by J. Thornton, Journal of Molecular Biology, vol.307, issue.5, pp.1419-1426, 2001.
DOI : 10.1006/jmbi.2001.4554

H. M. Berman, G. J. Kleywegt, H. Nakamura, and J. L. Markley, The Protein Data Bank at 40: Reflecting on the Past to Prepare for the Future, Structure, vol.20, issue.3, pp.391-396, 2012.
DOI : 10.1016/j.str.2012.01.010

R. M. Bhaskara and N. Srinivasan, Stability of domain structures in multi-domain proteins, Scientific Reports, vol.25, issue.1, p.40, 2011.
DOI : 10.1093/bioinformatics/btp242

R. E. Bird, K. D. Hardman, J. W. Jacobson, S. Johnson, B. M. Kaufman et al., Single-chain antigen-binding proteins, Science, vol.242, issue.4877, pp.423-426, 1988.
DOI : 10.1126/science.3140379

C. Bonet-costa, M. Vilaseca, C. Diema, O. Vujatovic, A. Vaquero et al., Combined bottom-up and top-down mass spectrometry analyses of the pattern of post-translational modifications of Drosophila melanogaster linker histone H1, Journal of Proteomics, vol.75, issue.13, pp.4124-4138, 2012.
DOI : 10.1016/j.jprot.2012.05.034

S. D. Briggs and T. E. Smithgall, SH2-Kinase Linker Mutations Release Hck Tyrosine Kinase and Transforming Activities in Rat-2 Fibroblasts, Journal of Biological Chemistry, vol.274, issue.37, pp.26579-26583, 1999.
DOI : 10.1074/jbc.274.37.26579

P. Chen, C. Liu, L. Burge, J. Li, M. Mohammad et al., DomSVR: domain boundary prediction with support vector regression from sequence information alone, Amino Acids, vol.285, issue.2, pp.713-726, 2010.
DOI : 10.1007/s00726-010-0506-6

S. Chung, J. B. Parker, M. Bianchet, L. M. Amzel, and J. T. Stivers, Impact of linker strain and flexibility in the design of a fragment-based inhibitor, Nature Chemical Biology, vol.72, issue.6, pp.407-413, 2009.
DOI : 10.1038/nchembio.163

A. G. De-brevern, New assessment of a structural alphabet, In Silico Biology, vol.5, pp.283-289, 2005.
URL : https://hal.archives-ouvertes.fr/inserm-00132875

A. G. De-brevern, C. Etchebest, and S. Hazout, Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks, Proteins: Structure, Function, and Genetics, vol.7, issue.3, pp.271-287, 2000.
DOI : 10.1002/1097-0134(20001115)41:3<271::AID-PROT10>3.0.CO;2-Z

URL : https://hal.archives-ouvertes.fr/inserm-00132821

A. G. De-brevern, H. Valadie, S. Hazout, and C. Etchebest, Extension of a local backbone description using a structural alphabet: A new approach to the sequence-structure relationship, Protein Science, vol.40, issue.(1/2), pp.2871-2886, 2002.
DOI : 10.1110/ps.0220502

URL : https://hal.archives-ouvertes.fr/inserm-00143374

B. L. De-groot, D. M. Van-aalten, R. M. Scheek, A. Amadei, G. Vriend et al., Prediction of protein conformational freedom from distance constraints, Proteins: Structure, Function, and Genetics, vol.26, issue.2, pp.240-251, 1997.
DOI : 10.1002/(SICI)1097-0134(199710)29:2<240::AID-PROT11>3.0.CO;2-O

Q. Dong, X. Wang, L. Lin, and Z. Xu, Domain boundary prediction based on profile domain linker propensity index, Computational Biology and Chemistry, vol.30, issue.2, pp.127-133, 2006.
DOI : 10.1016/j.compbiolchem.2006.01.001

D. L. Dowe, L. Allison, T. I. Dix, L. Hunter, C. S. Wallace et al., Circular clustering of protein dihedral angles by minimum message length, Pacific Symposium on Biocomputing, pp.242-255, 1996.

M. Dumontier, R. Yao, H. J. Feldman, and C. W. Hogue, Armadillo: Domain Boundary Prediction by Amino Acid Composition, Journal of Molecular Biology, vol.350, issue.5, pp.1061-1073, 2005.
DOI : 10.1016/j.jmb.2005.05.037

T. Ebina, H. Toh, and Y. Kuroda, Loop-length-dependent SVM prediction of domain linkers for high-throughput structural proteomics, Biopolymers, vol.7, issue.1, pp.1-8, 2009.
DOI : 10.1002/bip.21105

J. Eickholt, X. Deng, and J. Cheng, DoBo: Protein domain boundary prediction by integrating evolutionary signals and machine learning, BMC Bioinformatics, vol.12, issue.1, p.43, 2011.
DOI : 10.1186/1471-2105-12-43

URL : http://doi.org/10.1186/1471-2105-12-43

I. Ezkurdia, O. Grana, J. M. Izarzugaza, and M. L. Tress, Assessment of domain boundary predictions and the prediction of intramolecular contacts in CASP8, Proteins: Structure, Function, and Bioinformatics, vol.10, issue.Suppl 9, pp.77-196, 2009.
DOI : 10.1002/prot.22554

P. Fiorani, A. Bruselles, M. Falconi, G. Chillemi, A. Desideri et al., Single Mutation in the Linker Domain Confers Protein Flexibility and Camptothecin Resistance to Human Topoisomerase I, Journal of Biological Chemistry, vol.278, issue.44, pp.43268-43275, 2003.
DOI : 10.1074/jbc.M303899200

L. Fourrier, C. Benros, and A. G. De-brevern, Use of a structural alphabet for analysis of short loops connecting repetitive structures, BMC Bioinformatics, vol.5, issue.1, p.58, 2004.
DOI : 10.1186/1471-2105-5-58

URL : https://hal.archives-ouvertes.fr/inserm-00112104

D. Frishman and P. Argos, Knowledge-based protein secondary structure assignment, Proteins: Structure, Function, and Genetics, vol.206, issue.4, pp.566-579, 1995.
DOI : 10.1002/prot.340230412

M. Gao and J. Skolnick, iAlign: a method for the structural comparison of protein-protein interfaces, Bioinformatics, vol.26, issue.18, pp.2259-2265, 2010.
DOI : 10.1093/bioinformatics/btq404

J. C. Gelly, A. P. Joseph, N. Srinivasan, and A. G. De-brevern, iPBA: a tool for protein structure comparison using sequence alignment strategies, Nucleic Acids Research, vol.39, issue.suppl, pp.18-23, 2011.
DOI : 10.1093/nar/gkr333

URL : https://hal.archives-ouvertes.fr/inserm-00646241

R. A. George and J. Heringa, An analysis of protein domain linkers: their classification and role in protein folding, Protein Engineering Design and Selection, vol.15, issue.11, pp.871-879, 2002.
DOI : 10.1093/protein/15.11.871

R. S. Gokhale, S. Y. Tsuji, D. E. Cane, and C. Khosla, Dissecting and Exploiting Intermodular Communication in Polyketide Synthases, Science, vol.284, issue.5413, pp.482-485, 1999.
DOI : 10.1126/science.284.5413.482

J. H. Han, N. Kerrison, C. Chothia, and S. A. Teichmann, Divergence of Interdomain Geometry in Two-Domain Proteins, Structure, vol.14, issue.5, pp.935-945, 2006.
DOI : 10.1016/j.str.2006.01.016

H. Hasegawa and L. Holm, Advances and pitfalls of protein structural alignment, Current Opinion in Structural Biology, vol.19, issue.3, pp.341-348, 2009.
DOI : 10.1016/j.sbi.2009.04.003

M. Heinig and D. Frishman, STRIDE: a web server for secondary structure assignment from known atomic coordinates of proteins, Nucleic Acids Research, vol.32, issue.Web Server, pp.500-502, 2004.
DOI : 10.1093/nar/gkh429

L. Holm and C. Sander, Touring protein fold space with Dali/FSSP, Nucleic Acids Research, vol.26, issue.1, pp.316-319, 1998.
DOI : 10.1093/nar/26.1.316

URL : http://doi.org/10.1093/nar/26.1.316

M. Ikebe, T. Kambara, W. F. Stafford, M. Sata, E. Katayama et al., A Hinge at the Central Helix of the Regulatory Light Chain of Myosin Is Critical for Phosphorylation-dependent Regulation of Smooth Muscle Myosin Motor Activity, Journal of Biological Chemistry, vol.273, issue.28, pp.17702-17707, 1998.
DOI : 10.1074/jbc.273.28.17702

A. P. Joseph, G. Agarwal, S. Mahajan, J. C. Gelly, L. S. Swapna et al., A short survey on protein blocks, Biophysical Reviews, vol.30, issue.3, pp.137-147, 2010.
DOI : 10.1007/s12551-010-0036-1

URL : https://hal.archives-ouvertes.fr/inserm-00512823

G. Koczyk and I. N. Berezovsky, Domain Hierarchy and closed Loops (DHcL): a server for exploring hierarchy of protein domain structure, Nucleic Acids Research, vol.36, issue.Web Server, pp.239-245, 2008.
DOI : 10.1093/nar/gkn326

L. Kong and S. Ranganathan, Delineation of modular proteins: Domain boundary prediction from sequence information, Briefings in Bioinformatics, vol.5, issue.2, pp.179-192, 2004.
DOI : 10.1093/bib/5.2.179

M. Lu, J. Chai, and D. Fu, Structural basis for autoregulation of the zinc transporter YiiP, Nature Structural & Molecular Biology, vol.277, issue.10, pp.1063-1067, 2009.
DOI : 10.1107/S0907444996012255

Y. Maeda, H. Ueda, T. Hara, J. Kazami, G. Kawano et al., Expression of a bifunctional chimeric protein A-Vargula hilgendorfii luciferase in mammalian cells, BioTechniques, vol.20, pp.116-121, 1996.

A. D. Mclaclan, Rapid comparison of protein structures, Acta Crystallographica Section A, vol.38, issue.6, pp.871-873, 1982.
DOI : 10.1107/S0567739482001806

S. Miyazaki, Y. Kuroda, and S. Yokoyama, Identification of putative domain linkers by a neural network application to a large sequence database, BMC Bioinformatics, vol.7, issue.1, p.323, 2006.
DOI : 10.1186/1471-2105-7-323

G. Morra, R. Potestio, C. Micheletti, and G. Colombo, Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations, PLoS Computational Biology, vol.19, issue.3, p.1002433, 2012.
DOI : 10.1371/journal.pcbi.1002433.s019

A. G. Murzin, S. E. Brenner, T. Hubbard, and C. Chothia, SCOP: A structural classification of proteins database for the investigation of sequences and structures, Journal of Molecular Biology, vol.247, issue.4, pp.536-540, 1995.
DOI : 10.1016/S0022-2836(05)80134-2

W. Nomura, A. Masuda, K. Ohba, A. Urabe, N. Ito et al., Effects of DNA Binding of the Zinc Finger and Linkers for Domain Fusion on the Catalytic Activity of Sequence-Specific Chimeric Recombinases Determined by a Facile Fluorescent System, Biochemistry, vol.51, issue.7, pp.1510-1517, 2012.
DOI : 10.1021/bi201878x

J. Schymkowitz, J. Borg, F. Stricher, R. Nys, F. Rousseau et al., The FoldX web server: an online force field, Nucleic Acids Research, vol.33, issue.Web Server, pp.382-388, 2005.
DOI : 10.1093/nar/gki387

C. J. Strang, M. E. Wales, D. M. Brown, and J. R. Wild, Site-directed alterations to the geometry of the aspartate transcarbamoylase zinc domain: Selective alteration to regulation by heterotropic ligands, isoelectric point, and stability in urea, Biochemistry, vol.32, issue.16, pp.4156-4167, 1993.
DOI : 10.1021/bi00067a002

M. Takizawa, K. Miyauchi, E. Urano, S. Kusagawa, K. Kitamura et al., Regulation of the susceptibility of HIV-1 to a neutralizing antibody KD-247 by nonepitope mutations distant from its epitope, AIDS, vol.25, issue.18, pp.2209-2216, 2011.
DOI : 10.1097/QAD.0b013e32834bab68

Y. Tang, N. Jiang, C. Parakh, and D. Hilvert, Selection of linkers for a catalytic single-chain antibody using phage display technology, Journal of Biological Chemistry, vol.271, pp.15682-15686, 1996.

T. W. Traut, Enzymes of Nucleotide Metabolism: The Significance of Subunit Size and Polymer Size for Biological Function and Regulatory Propertie, Critical Reviews in Biochemistry, vol.3, issue.2, pp.121-169, 1988.
DOI : 10.1128/MCB.5.12.3443

G. Valentini, L. Chiarelli, R. Fortin, M. L. Speranza, A. Galizzi et al., The Allosteric Regulation of Pyruvate Kinase. A SITE-DIRECTED MUTAGENESIS STUDY, Journal of Biological Chemistry, vol.275, issue.24, pp.18145-18152, 2000.
DOI : 10.1074/jbc.M001870200

J. Van-durme, J. Delgado, F. Stricher, L. Serrano, J. Schymkowitz et al., A graphical interface for the FoldX forcefield, Bioinformatics, vol.27, issue.12, pp.1711-1712, 2011.
DOI : 10.1093/bioinformatics/btr254

H. C. Van-leeuwen, M. J. Strating, M. Rensen, W. De-laat, and P. C. Van-der-vliet, Linker length and composition influence the flexibility of Oct-1 DNA binding, The EMBO Journal, vol.16, issue.8, pp.2043-2053, 1997.
DOI : 10.1093/emboj/16.8.2043

F. K. Winkler, C. E. Schutt, S. C. Harrison, and G. Bricogne, Tomato bushy stunt virus at 5.5-??? resolution, Nature, vol.261, issue.5594, pp.509-513, 1977.
DOI : 10.1038/265509a0

W. Wriggers, S. Chakravarty, and P. A. Jennings, Control of protein functional dynamics by peptide linkers, Biopolymers, vol.23, issue.6, pp.736-746, 2005.
DOI : 10.1002/bip.20291

P. D. Yoo, A. R. Sikder, J. Taheri, B. B. Zhou, and A. Y. Zomaya, DomNet: Protein Domain Boundary Prediction Using Enhanced General Regression Network and New Profiles, IEEE Transactions on NanoBioscience, vol.7, issue.2, pp.172-181, 2008.
DOI : 10.1109/TNB.2008.2000747

P. D. Yoo, A. R. Sikder, B. B. Zhou, and A. Y. Zomaya, Improved general regression network for protein domain boundary prediction, BMC Bioinformatics, vol.9, issue.Suppl 1, p.12, 2008.
DOI : 10.1186/1471-2105-9-S1-S12

URL : http://doi.org/10.1186/1471-2105-9-s1-s12

A. Zemla, LGA: a method for finding 3D similarities in protein structures, Nucleic Acids Research, vol.31, issue.13, pp.3370-3374, 2003.
DOI : 10.1093/nar/gkg571

Y. Zhang, B. Liu, Q. Dong, and V. X. Jin, An Improved Profile-Level Domain Linker Propensity Index for Protein Domain Boundary Prediction., Protein & Peptide Letters, vol.18, issue.1, pp.7-16, 2011.
DOI : 10.2174/092986611794328717