{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:46:59Z","timestamp":1760975219487},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,9,29]],"date-time":"2003-09-29T00:00:00Z","timestamp":1064793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopolymers"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Titin, a family of giant elastic proteins, constitutes an elastic sarcomere matrix in striated muscle. In the I\u2010band region of the sarcomere, the titin PEVK segment acts as a molecular spring to generate elasticity as well as sites of adhesion with parallel thin filaments. Previously, we reported that PEVK consists of tandem repeats of 28 residue modules and that the \u201cpolyproline II\u2010coil\u201d motif is the fundamental conformational motif of the PEVK module. In order to characterize the factors that may affect and alter the PPII\u2010coil conformational motifs, we have initiated a systematic study of the interaction with divalent cations (Cu<jats:sup>2+<\/jats:sup>, Ca<jats:sup>2+<\/jats:sup>, Zn<jats:sup>2+<\/jats:sup>, and Ni<jats:sup>2+<\/jats:sup>) and a conformational profile of PEVK peptides (a representative 28\u2010mer peptide PR: PEPPKEVVPEKKAPVAPPKKPEVPPVKV and its subfragments PR1: kvPEPPKEVVPE, PR2: VPEKKAPVAPPK, PR3: KPEVPPVKV). UV\u2010Vis absorption difference spectra and CD spectra showed that Cu<jats:sup>2+<\/jats:sup> bound to PR1 with high affinity (20 \u03bc<jats:italic>M<\/jats:italic>), while its binding to PR2 and PR3 as well as the binding of other cations to all four peptides were of lower affinity (&gt;100 \u03bc<jats:italic>M<\/jats:italic>). Conformational studies by CD revealed that Cu<jats:sup>2+<\/jats:sup> binding to PR1 resulted in a polyproline II to turn transition up to a 1:2 PR1\/Cu<jats:sup>2+<\/jats:sup> ratio and a coil to turn transition at higher Cu<jats:sup>2+<\/jats:sup> concentration. ESI\u2010MS provided the stoichiometry of PEVK peptide\u2010Cu<jats:sup>2+<\/jats:sup> complexes at both low and high ion strength, confirming the specific high affinity binding of Cu<jats:sup>2+<\/jats:sup> to PR1 and PR. Furthermore, NMR and ESI\u2010MS\/MS fragmentation analysis elucidated the binding sites of the PEVK peptide\u2010Cu<jats:sup>2+<\/jats:sup> complexes at <jats:sup>\u22122<\/jats:sup>KVPE<jats:sup>2<\/jats:sup>, <jats:sup>8<\/jats:sup>VPE<jats:sup>10<\/jats:sup>, <jats:sup>13<\/jats:sup>APV<jats:sup>15<\/jats:sup>, and <jats:sup>22<\/jats:sup>EVP<jats:sup>24<\/jats:sup>. A potential application of Cu<jats:sup>2+<\/jats:sup> binding in peptide sequencing by mass spectrometry was also revealed. We conclude that Cu<jats:sup>2+<\/jats:sup> binds and bends PEVK peptides to a beta\u2010turn\u2010like structure at specific sites. The specific targeting of Cu<jats:sup>2+<\/jats:sup> towards PPII is likely to be of significant value in elucidating the roles of PPII in titin elasticity as well as in interactions of proline\u2010rich proteins. \u00a9 2003 Wiley Periodicals, Inc. Biopolymers 70: 297\u2013309, 2003<\/jats:p>","DOI":"10.1002\/bip.10477","type":"journal-article","created":{"date-parts":[[2003,10,22]],"date-time":"2003-10-22T19:29:56Z","timestamp":1066850996000},"page":"297-309","source":"Crossref","is-referenced-by-count":14,"title":["Binding of copper(II) ions to the polyproline II helices of PEVK modules of the giant elastic protein titin as revealed by ESI\u2010MS, CD, and NMR"],"prefix":"10.1002","volume":"70","author":[{"given":"Kan","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,9,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-227X(96)81668-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02346660"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01641-4"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(01)00009-8"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5234.293"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100981"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008851200"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0134(20010501)43:2<145::AID-PROT1026>3.0.CO;2-B"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0022792"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75876-6"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03655-4"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.38.717"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng815"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6448"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng816"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.6.H1840"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.2.H476"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/4.6.669"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(92)90046-A"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2364(85)90018-6"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2364(85)90171-4"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2364(88)90178-3"},{"key":"e_1_2_6_24_2","volume-title":"Advanced Inorganic Chemistry","author":"Cotton F. 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