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Plasminogen is used as a detailed case study.",{"type":9,"tag":45,"props":1427,"children":1429},{"id":1428},"plasminogen-architecture-figure-55",[1430],{"type":15,"value":1431},"Plasminogen architecture (Figure 55)",{"type":9,"tag":57,"props":1433,"children":1434},{},[1435,1440,1470],{"type":9,"tag":61,"props":1436,"children":1437},{},[1438],{"type":15,"value":1439},"791 aa precursor of plasmin.",{"type":9,"tag":61,"props":1441,"children":1442},{},[1443,1445],{"type":15,"value":1444},"Contains:",{"type":9,"tag":57,"props":1446,"children":1447},{},[1448,1459],{"type":9,"tag":61,"props":1449,"children":1450},{},[1451,1453,1458],{"type":15,"value":1452},"N-terminal region + ",{"type":9,"tag":22,"props":1454,"children":1455},{},[1456],{"type":15,"value":1457},"five kringle domains (1–5)",{"type":15,"value":773},{"type":9,"tag":61,"props":1460,"children":1461},{},[1462,1464,1469],{"type":15,"value":1463},"plus a ",{"type":9,"tag":22,"props":1465,"children":1466},{},[1467],{"type":15,"value":1468},"trypsin-like serine protease domain",{"type":15,"value":154},{"type":9,"tag":61,"props":1471,"children":1472},{},[1473],{"type":15,"value":1474},"Various fragments (kringles 1–3, kringle 4, kringle 5–protease “miniplasminogen”) can be produced by elastase cleavage and studied separately.",{"type":9,"tag":45,"props":1476,"children":1478},{"id":1477},"castellino-et-al-at-ph-74-figure-56-complex-partly-irreversible-behavior",[1479],{"type":15,"value":1480},"Castellino et al. at pH 7.4 (Figure 56): complex, partly irreversible behavior",{"type":9,"tag":57,"props":1482,"children":1483},{},[1484,1496,1501,1513],{"type":9,"tag":61,"props":1485,"children":1486},{},[1487,1489,1494],{"type":15,"value":1488},"Intact plasminogen shows a ",{"type":9,"tag":22,"props":1490,"children":1491},{},[1492],{"type":15,"value":1493},"broad",{"type":15,"value":1495}," melting curve → multiple overlapping transitions.",{"type":9,"tag":61,"props":1497,"children":1498},{},[1499],{"type":15,"value":1500},"Individual fragments show simpler (but still broad) patterns.",{"type":9,"tag":61,"props":1502,"children":1503},{},[1504,1506,1511],{"type":15,"value":1505},"Adding ligand ",{"type":9,"tag":22,"props":1507,"children":1508},{},[1509],{"type":15,"value":1510},"ε-aminocaproic acid",{"type":15,"value":1512}," raises Tm values and changes transitions—implying ligand interactions across fragments.",{"type":9,"tag":61,"props":1514,"children":1515},{},[1516,1518,1523],{"type":15,"value":1517},"But interpretation is limited because transitions were ",{"type":9,"tag":22,"props":1519,"children":1520},{},[1521],{"type":15,"value":1522},"not fully reversible",{"type":15,"value":1524},", with insoluble denatured protein forming.",{"type":9,"tag":45,"props":1526,"children":1528},{"id":1527},"novokhatny-et-al-at-ph-34-figure-57-cleaner-reversible-transitions-stronger-conclusions",[1529],{"type":15,"value":1530},"Novokhatny et al. at pH 3.4 (Figure 57): cleaner, reversible transitions → stronger conclusions",{"type":9,"tag":18,"props":1532,"children":1533},{},[1534],{"type":15,"value":1535},"At low pH where transitions were reversible:",{"type":9,"tag":57,"props":1537,"children":1538},{},[1539,1544,1562,1567,1579],{"type":9,"tag":61,"props":1540,"children":1541},{},[1542],{"type":15,"value":1543},"Intact plasminogen: multiple close melting transitions.",{"type":9,"tag":61,"props":1545,"children":1546},{},[1547,1549,1554,1556,1561],{"type":15,"value":1548},"Kringles 1–3: deconvolution suggests ",{"type":9,"tag":22,"props":1550,"children":1551},{},[1552],{"type":15,"value":1553},"three transitions",{"type":15,"value":1555}," → each kringle unfolds like an ",{"type":9,"tag":22,"props":1557,"children":1558},{},[1559],{"type":15,"value":1560},"independent folding unit",{"type":15,"value":154},{"type":9,"tag":61,"props":1563,"children":1564},{},[1565],{"type":15,"value":1566},"Kringle 1 alone confirms “miniprotein-like” independent behavior.",{"type":9,"tag":61,"props":1568,"children":1569},{},[1570,1572,1577],{"type":15,"value":1571},"Kringle 5 + serine protease: suggests ",{"type":9,"tag":22,"props":1573,"children":1574},{},[1575],{"type":15,"value":1576},"three components",{"type":15,"value":1578},"; kringle 5 corresponds to one lower-temperature transition, and the protease contributes two (consistent with the protease having two domains).",{"type":9,"tag":61,"props":1580,"children":1581},{},[1582,1584,1589],{"type":15,"value":1583},"Overall message: at pH 3.4, plasminogen behaves like ",{"type":9,"tag":22,"props":1585,"children":1586},{},[1587],{"type":15,"value":1588},"modular beads-on-a-string",{"type":15,"value":1590}," (weak interdomain coupling).",{"type":9,"tag":18,"props":1592,"children":1593},{},[1594],{"type":15,"value":1595},"They note that at physiological pH (7.4) plasminogen likely has stronger interdomain interactions and a different overall shape—still flexible, and influenced by ligand binding to kringles (e.g., C-terminal Lys on fibrin fragments).",1775084292167]