Abstract
About half of the globular proteins are composed of regular secondary structures, α-helices, and β-sheets, while the rest are constituted of irregular secondary structures, such as turns or coil conformations. Other regular secondary structures are often ignored, despite their importance in biological processes. Among such structures, the polyproline II helix (PPII) has interesting behaviours. PPIIs are not usually associated with conventional stabilizing interactions, and recent studies have observed that PPIIs are more frequent than anticipated. In addition, it is suggested that they may have an important functional role, particularly in protein–protein or protein–nucleic acid interactions and recognition. Residues associated with PPII conformations represent nearly 5% of the total residues, but the lack of PPII assignment approaches prevents their systematic analysis. This short review will present current knowledge and recent research in PPII area. In a first step, the different methodologies able to assign PPII are presented. In the second step, recent studies that have shown new perspectives in PPII analysis in terms of structure and function are underlined with three cases: (1) PPII in protein structures. For instance, the first crystal structure of an oligoproline adopting an all-trans polyproline II (PPII) helix had been presented; (2) the involvement of PPII in different diseases and drug designs; and (3) an interesting extension of PPII study in the protein dynamics. For instance, PPIIs are often linked to disorder region analysis and the precise analysis of a potential PPII helix in hypogonadism shows unanticipated PPII formations in the patient mutation, while it is not observed in the wild-type form of KISSR1 protein.
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References
Adzhubei AA, Sternberg MJ (1993) Left-handed polyproline II helices commonly occur in globular proteins. J Mol Biol 229:472–493. doi:10.1006/jmbi.1993.1047
Adzhubei AA, Sternberg MJ, Makarov AA (2013) Polyproline-II helix in proteins: structure and function. J Mol Biol 425:2100–2132. doi:10.1016/j.jmb.2013.03.018
Adzhubei AA, Anashkina AA, Makarov AA (2016) Left-handed polyproline-II helix revisited: proteins causing proteopathies. J Biomol Struct Dyn. doi:10.1080/07391102.2016.1229220
Agrawal V, Kishan KV (2002) Promiscuous binding nature of SH3 domains to their target proteins. Protein Pept Lett 9:185–193
Aksianov E, Alexeevski A (2012) SheeP: a tool for description of beta-sheets in protein 3D structures. J Bioinform Comput Biol 10:1241003. doi:10.1142/S021972001241003X
Arnott S, Dover SD (1968) The structure of poly-l-proline II. Acta Crystallogr B 24:599–601
Bansal M, Kumar S, Velavan R (2000) HELANAL: a program to characterize helix geometry in proteins. J Biomol Struct Dyn 17:811–819. doi:10.1080/07391102.2000.10506570
Bella J, Eaton M, Brodsky B, Berman HM (1994) Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. Science 266:75–81
Berman HM et al (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242
Bernstein FC et al (1977) The protein data bank: a computer-based archival file for macromolecular structures. J Mol Biol 112:535–542
Blanch EW, Morozova-Roche LA, Cochran DA, Doig AJ, Hecht L, Barron LD (2000) Is polyproline II helix the killer conformation? A Raman optical activity study of the amyloidogenic prefibrillar intermediate of human lysozyme. J Mol Biol 301:553–563. doi:10.1006/jmbi.2000.3981
Bochicchio B, Tamburro AM (2002) Polyproline II structure in proteins: identification by chiroptical spectroscopies, stability, and functions. Chirality 14:782–792. doi:10.1002/chir.10153
Booker GW, Breeze AL, Downing AK, Panayotou G, Gout I, Waterfield MD, Campbell ID (1992) Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase. Nature 358:684–687. doi:10.1038/358684a0
Bornot A, de Brevern AG (2006) Protein beta-turn assignments. Bioinformation 1:153–155
Cao C, Wang G, Liu A, Xu S, Wang L, Zou S (2016) A new secondary structure assignment algorithm using calpha backbone fragments. Int J Mol Sci 17:333. doi:10.3390/ijms17030333
Carter P, Andersen CA, Rost B (2003) DSSPcont: continuous secondary structure assignments for proteins. Nucleic Acids Res 31:3293–3295
Carugo O, Djinovic-Carugo K (2013) Half a century of Ramachandran plots. Acta Crystallogr D Biol Crystallogr 69:1333–1341. doi:10.1107/S090744491301158X
Chebrek R, Leonard S, de Brevern AG, Gelly JC (2014) PolyprOnline: polyproline helix II and secondary structure assignment database Database (Oxford) 2014 doi:10.1093/database/bau102
Chevrier L, de Brevern A, Hernandez E, Leprince J, Vaudry H, Guedj AM, de Roux N (2013) PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane. Mol Endocrinol 27:1004–1014. doi:10.1210/me.2012-1386
Cowan PM, McGavin S, North AC (1955) The polypeptide chain configuration of collagen. Nature 176:1062–1064
Creamer TP (1998) Left-handed polyproline II helix formation is (very) locally driven. Proteins 33:218–226
Cubellis MV, Caillez F, Blundell TL, Lovell SC (2005a) Properties of polyproline II, a secondary structure element implicated in protein-protein interactions. Proteins 58:880–892. doi:10.1002/prot.20327
Cubellis MV, Cailliez F, Lovell SC (2005b) Secondary structure assignment that accurately reflects physical and evolutionary characteristics. BMC Bioinform 6(Suppl 4):S8. doi:10.1186/1471-2105-6-S4-S8
Delano WL (2013) The PyMOL molecular graphics system on World Wide Web. http://www.pymol.org. Accessed 3 Jan 2017
Dupuis F, Sadoc JF, Mornon JP (2004) Protein secondary structure assignment through Voronoi tessellation. Proteins 55:519–528. doi:10.1002/prot.10566
Eiriksdottir E, Konate K, Langel U, Divita G, Deshayes S (2010) Secondary structure of cell-penetrating peptides controls membrane interaction and insertion. Biochim Biophys Acta 1798:1119–1128. doi:10.1016/j.bbamem.2010.03.005
Eisenberg D (2003) The discovery of the alpha-helix and beta-sheet, the principal structural features of proteins. Proc Natl Acad Sci USA 100:11207–11210
Ferreon JC, Hilser VJ (2003) The effect of the polyproline II (PPII) conformation on the denatured state entropy. Protein Sci 12:447–457. doi:10.1110/ps.0237803
Fillon YA, Anderson JP, Chmielewski J (2005) Cell penetrating agents based on a polyproline helix scaffold. J Am Chem Soc 127:11798–11803. doi:10.1021/ja052377g
Fodje MN, Al-Karadaghi S (2002) Occurrence, conformational features and amino acid propensities for the pi-helix. Protein Eng 15:353–358
Foged C, Nielsen HM (2008) Cell-penetrating peptides for drug delivery across membrane barriers. Expert Opin Drug Deliv 5:105–117. doi:10.1517/17425247.5.1.105
Franz J, Lelle M, Peneva K, Bonn M, Weidner T (2016) SAP(E)—a cell-penetrating polyproline helix at lipid interfaces. Biochim Biophys Acta 1858:2028–2034. doi:10.1016/j.bbamem.2016.05.021
Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins 23:566–579. doi:10.1002/prot.340230412
Geisler I, Chmielewski J (2009) Cationic amphiphilic polyproline helices: side-chain variations and cell-specific internalization. Chem Biol Drug Des 73:39–45. doi:10.1111/j.1747-0285.2008.00759.x
Hicks JM, Hsu VL (2004) The extended left-handed helix: a simple nucleic acid-binding motif. Proteins 55:330–338. doi:10.1002/prot.10630
Hosseini SR, Sadeghi M, Pezeshk H, Eslahchi C, Habibi M (2008) PROSIGN: a method for protein secondary structure assignment based on three-dimensional coordinates of consecutive C(alpha) atoms. Comput Biol Chem 32:406–411. doi:10.1016/j.compbiolchem.2008.07.027
Hutchinson EG, Thornton JM (1996) PROMOTIF—a program to identify and analyze structural motifs in proteins. Protein Sci 5:212–220. doi:10.1002/pro.5560050204
Jha AK, Colubri A, Zaman MH, Koide S, Sosnick TR, Freed KF (2005) Helix, sheet, and polyproline II frequencies and strong nearest neighbor effects in a restricted coil library. Biochemistry 44:9691–9702. doi:10.1021/bi0474822
Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637. doi:10.1002/bip.360221211
King SM, Johnson WC (1999) Assigning secondary structure from protein coordinate data. Proteins 35:313–320
Kneller GR, Hinsen K (2015) Protein secondary-structure description with a coarse-grained model. Acta Crystallogr D Biol Crystallogr 71:1411–1422. doi:10.1107/S1399004715007191
Koleske AJ, Buratowski S, Nonet M, Young RA (1992) A novel transcription factor reveals a functional link between the RNA polymerase II CTD and TFIID. Cell 69:883–894
Kumar P, Bansal M (2015) Identification of local variations within secondary structures of proteins. Acta Crystallogr D Biol Crystallogr 71:1077–1086. doi:10.1107/S1399004715003144
Kumar P, Bansal M (2016) Structural and functional analyses of PolyProline-II helices in globular proteins. J Struct Biol 196:414–425. doi:10.1016/j.jsb.2016.09.006
Labesse G, Colloc’h N, Pothier J, Mornon JP (1997) P-SEA: a new efficient assignment of secondary structure from C alpha trace of proteins. Comput Appl Biosci 13:291–295
Law SM, Frank AT, Brooks CL 3rd (2014) PCASSO: a fast and efficient Calpha-based method for accurately assigning protein secondary structure elements. J Comput Chem 35:1757–1761. doi:10.1002/jcc.23683
Lewis HA, Musunuru K, Jensen KB, Edo C, Chen H, Darnell RB, Burley SK (2000) Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. Cell 100:323–332
Li L, Geisler I, Chmielewski J, Cheng JX (2010) Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria. J Control Release 142:259–266. doi:10.1016/j.jconrel.2009.10.012
Majumdar I, Krishna SS, Grishin NV (2005) PALSSE: a program to delineate linear secondary structural elements from protein structures. BMC Bioinformatics 6:202. doi:10.1186/1471-2105-6-202
Mansiaux Y, Joseph AP, Gelly JC, de Brevern AG (2011) Assignment of polyproline II conformation and analysis of sequence–structure relationship. PLoS One 6:e18401. doi:10.1371/journal.pone.0018401
Martin J, Letellier G, Marin A, Taly JF, de Brevern AG, Gibrat JF (2005) Protein secondary structure assignment revisited: a detailed analysis of different assignment methods. BMC Struct Biol 5:17. doi:10.1186/1472-6807-5-17
Offmann B, Tyagi M, de Brevern AG (2007) Local protein structures. Curr Bioinform 3:165–202
Oluwatobi Salawu E (2016) RaFoSA: random forests secondary structure assignment for coarse-grained and all-atom protein systems. Cogent Biol 2:1214061
Parisien M, Major F (2005) A new catalog of protein beta-sheets proteins 61:545–558. doi:10.1002/prot.20677
Park SY, Yoo MJ, Shin J, Cho KH (2011) SABA (secondary structure assignment program based on only alpha carbons): a novel pseudo center geometrical criterion for accurate assignment of protein secondary structures. BMB Rep 44:118–122. doi:10.5483/BMBRep
Pauling L, Corey RB (1950) Two hydrogen-bonded spiral configurations of the polypetide chain. J Am Chem Soc 72:5349
Pauling L, Corey RB (1951a) The pleated sheet, a new layer configuration of polypeptide chains. Proc Natl Acad Sci USA 37:251–256
Pauling L, Corey RB (1951b) The structure of fibrous proteins of the collagen-gelatin group. Proc Natl Acad Sci USA 37:272–281
Pauling L, Corey RB, Branson HR (1951) The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci USA 37:205–211
Pronk S et al (2013) GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29:845–854. doi:10.1093/bioinformatics/btt055
R Core Team (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) Stereochemistry of polypeptide chain configurations. J Mol Biol 7:95–99
Rich A, Crick FH (1955) The structure of collagen. Nature 176:915–916
Richards FM, Kundrot CE (1988) Identification of structural motifs from protein coordinate data: secondary structure and first-level supersecondary structure. Proteins 3:71–84. doi:10.1002/prot.340030202
Richardson JS (1981) The anatomy and taxonomy of protein structure. Adv Protein Chem 34:167–339
Rose GD (1978) Prediction of chain turns in globular proteins on a hydrophobic basis. Nature 272:586–590
Ruzza P, Calderan A, Guiotto A, Osler A, Borin G (2004) Tat cell-penetrating peptide has the characteristics of a poly(proline) II helix in aqueous solution and in SDS micelles. J Pept Sci 10:423–426. doi:10.1002/psc.558
Sasisekharan V (1959) Structure of poly-l-proline II. Acta Crystallogr 12:897–903
Shakarji CM (1998) Least-squares fitting algorithms of the NIST algorithm testing system. J Res Natl Inst Stand Technol 103:633
Sklenar H, Etchebest C, Lavery R (1989) Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis. Proteins 6:46–60. doi:10.1002/prot.340060105
Soman KV, Ramakrishnan C (1983) Occurrence of a single helix of the collagen type in globular proteins. J Mol Biol 170:1045–1048
Sreerama N, Woody RW (1994) Poly(pro)II helices in globular proteins: identification and circular dichroic analysis. Biochemistry 33:10022–10025
Sreerama N, Woody RW (2003) Structural composition of betaI- and betaII-proteins. Protein Sci 12:384–388. doi:10.1110/ps.0235003
Srinivasan R, Rose GD (1999) A physical basis for protein secondary structure. Proc Natl Acad Sci USA 96:14258–14263
Stapley BJ, Creamer TP (1999) A survey of left-handed polyproline II helices. Protein Sci 8:587–595. doi:10.1110/ps.8.3.587
Sugeta H, Miyazawa T (1967) General method for calculating helical parameters of polymer chains from bond lengths, bond angles, and internal-rotation angles. Biopolymers 5:673–679
Suzuki M (1989) SPXX, a frequent sequence motif in gene regulatory proteins. J Mol Biol 207:61–84
Suzuki M, Sohma H, Yazawa M, Yagi K, Ebashi S (1990) Histone H1 kinase specific to the SPKK motif. J Biochem 108:356–364
Syme CD, Blanch EW, Holt C, Jakes R, Goedert M, Hecht L, Barron LD (2002) A Raman optical activity study of rheomorphism in caseins, synucleins and tau. New insight into the structure and behaviour of natively unfolded proteins. Eur J Biochem 269:148–156
Toal S, Schweitzer-Stenner R (2014) Local order in the unfolded state: conformational biases and nearest neighbor interactions. Biomolecules 4:725–773. doi:10.3390/biom4030725
Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718. doi:10.1002/jcc.20291
Venkatachalam CM (1968) Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 6:1425–1436
Whittington SJ, Chellgren BW, Hermann VM, Creamer TP (2005) Urea promotes polyproline II helix formation: implications for protein denatured states. Biochemistry 44:6269–6275. doi:10.1021/bi050124u
Williamson MP (1994) The structure and function of proline-rich regions in proteins. Biochem J 297(Pt 2):249–260
Yamashita H et al (2016) Development of a cell-penetrating peptide that exhibits responsive changes in its secondary structure in the cellular environment. Sci Rep 6:33003. doi:10.1038/srep33003
Zacharias J, Knapp EW (2014) Protein secondary structure classification revisited: processing DSSP information with PSSC. J Chem Inf Model 54:2166–2179. doi:10.1021/ci5000856
Zhang Y, Sagui C (2015) Secondary structure assignment for conformationally irregular peptides: comparison between DSSP, STRIDE and KAKSI. J Mol Graph Model 55:72–84. doi:10.1016/j.jmgm.2014.10.005
Acknowledgements
We would like to thank Catherine Etchebest for fruitful discussions. This work was supported by grants from the Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), and labex GR-Ex. The labex GR-Ex, reference ANR-11-LABX-0051 is funded by the program “Investissements d’avenir” of the French National Research Agency, reference ANR-11-IDEX-0005-02. TjrN, NSr, and AdB acknowledge to Indo-French Centre for the Promotion of Advanced Research/CEFIPRA for collaborative grant (number 5302-2). NSh acknowledges support from ANRT (CIFRE convention number 2015/0832). NSr acknowledges for J.C. Bose fellowship and general support from DBT. AMV is supported by Allocations Regionales de Researche grant from Region Reunion.
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Narwani, T.J., Santuz, H., Shinada, N. et al. Recent advances on polyproline II. Amino Acids 49, 705–713 (2017). https://doi.org/10.1007/s00726-017-2385-6
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DOI: https://doi.org/10.1007/s00726-017-2385-6