1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biochemistry
  4. Volume 67, 1998
  5. Article

Annual Review of Biochemistry

Volume 67, 1998

BIOCHEMISTRY AND GENETICS OF VON WILLEBRAND FACTOR

Abstract

Von Willebrand factor (VWF) is a blood glycoprotein that is required for normal hemostasis, and deficiency of VWF, or von Willebrand disease (VWD), is the most common inherited bleeding disorder. VWF mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet membrane glycoproteins and to constituents of exposed connective tissue. These activities appear to be regulated by allosteric mechanisms and possibly by hydrodynamic shear forces. VWF also is a carrier protein for blood clotting factor VIII, and this interaction is required for normal factor VIII survival in the circulation. VWF is assembled from identical ≈250 kDa subunits into disulfide-linked multimers that may be >20,000 kDa. Mutations in VWD can disrupt this complex biosynthetic process at several steps to impair the assembly, intracellular _targeting, or secretion of VWF multimers. Other VWD mutations impair the survival of VWF in plasma or the function of specific ligand binding sites. This growing body of information about VWF synthesis, structure, and function has allowed the reclassification of VWD based upon distinct pathophysiologic mechanisms that appear to correlate with clincial symptoms and the response to therapy.

Keyword(s): factor VIII, hemostasis, platelet adhesion, von Willebrand disease, Weibel-Palade body
Loading

Article metrics loading...

/content/journals/10.1146/annurev.biochem.67.1.395
1998-07-01
2024-12-14
Loading full text...

Full text loading...

/deliver/fulltext/biochem/67/1/annurev.biochem.67.1.395.html?itemId=/content/journals/10.1146/annurev.biochem.67.1.395&mimeType=html&fmt=ahah

Literature Cited

  1. von Willebrand EA. 1926. Fin. Laekaresaellsk. Hand. 68:87–112 [Google Scholar]
  2. von Willebrand EA, Jürgens R. 1933. Dtsch. Arch. Klin. Med. 175:453–83 [Google Scholar]
  3. Alexander B, Goldstein B. 1953. J. Clin. Invest. 32:551 [Google Scholar]
  4. Larrieu MJ, Soulier JP. 1953. Rev. Hematol. 8:361–70 [Google Scholar]
  5. Quick AJ, Hussey CV. 1953. J. Lab. Clin. Med. 42:929–30 [Google Scholar]
  6. Nilsson IM, Blombäck M, von Francken I. 1957. Acta Med. Scand. 159:35–37 [Google Scholar]
  7. Nilsson IM, Blombäck M, Jorpes E, Blombäck B, Johansson S-A. 1957. Acta Med. Scand. 159:179–88 [Google Scholar]
  8. Sadler JE. 1995. In The Metabolic and Molecular Basis of Inherited Disease, ed. CR Scriver, AL Beaudet, WS Sly, D Valle 3269–87 New York: McGraw-Hill
  9. Jaffe EA, Hoyer LW, Nachman RL. 1974. Proc. Natl. Acad. Sci. USA 71:1906–9 [Google Scholar]
  10. Nachman R, Levine R, Jaffe EA. 1977. J. Clin. Invest. 60:914–21 [Google Scholar]
  11. Marti T, Rösselet SJ, Titani K, Walsh KA. 1987. Biochemistry 26:8099–109 [Google Scholar]
  12. Carew JA, Browning PJ, Lynch DC. 1990. Blood 76:2530–39 [Google Scholar]
  13. Matsui T, Titani K, Mizuochi T. 1992. J. Biol. Chem. 267:8723–31 [Google Scholar]
  14. Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H. 1991. J. Cell Biol. 113:195–205 [Google Scholar]
  15. McDonald NQ, Hendrickson WA. 1993. Cell 73:421–24 [Google Scholar]
  16. Meitinger T, Meindl A, Bork P, Rost B, Sander C. et al. 1993. Nat. Genet. 5:376–80 [Google Scholar]
  17. Desseyn J-L, Aubert JP, Van Seuningen I, Porchet N, Laine A. 1997. J. Biol. Chem. 272:16873–83 [Google Scholar]
  18. Schneppenheim R, Brassard J, Krey S, Budde U, Kunicki TJ. et al. 1996. Proc. Natl. Acad. Sci. USA 93:3581–86 [Google Scholar]
  19. Wagner DD, Mayadas T, Marder VJ. 1986. J. Cell Biol. 102:1320–24 [Google Scholar]
  20. Wagner DD, Saffaripour S, Bonfanti R, Sadler JE, Cramer EM. et al. 1991. Cell 64:403–13 [Google Scholar]
  21. Rehemtulla A, Kaufman RJ. 1992. Blood 79:2349–55 [Google Scholar]
  22. Vischer UM, Wagner DD. 1994. Blood 83:3536–44 [Google Scholar]
  23. Voorberg J, Fontijn R, van Mourik JA, Pannekoek H. 1990. EMBO J. 9:797–803 [Google Scholar]
  24. Verweij CL, Hart M, Pannekoek H. 1987. EMBO J. 6:2885–90 [Google Scholar]
  25. Wise RJ, Pittman DD, Handin RI, Kaufman RJ, Orkin SH. 1988. Cell 52:229–36 [Google Scholar]
  26. Verweij CL, Hart M, Pannekoek H. 1988. J. Biol. Chem. 263:7921–24 [Google Scholar]
  27. Mayadas TN, Wagner DD. 1989. J. Biol. Chem. 264:13497–503 [Google Scholar]
  28. Mayadas TN, Wagner DD. 1992. Proc. Natl. Acad. Sci. USA 89:3531–35 [Google Scholar]
  29. Fujimura Y, Titani K, Holland LZ, Russell SR, Roberts JR. et al. 1986. J. Biol. Chem. 261:381–85 [Google Scholar]
  30. Dong Z, Thoma RS, Crimmins DL, McCourt DW, Tuley EA, Sadler JE. 1994. J. Biol. Chem. 269:6753–58 [Google Scholar]
  31. Wagner DD, Olmsted JB, Marder VJ. 1982. J. Cell Biol. 95:355–60 [Google Scholar]
  32. Sporn LA, Marder VJ, Wagner DD. 1986. Cell 46:185–90 [Google Scholar]
  33. Weibel ER, Palade GE. 1964. J. Cell Biol. 23:101–12 [Google Scholar]
  34. Cramer EM, Meyer D, le Menn R, Breton-Gorius J. 1985. Blood 66:710–13 [Google Scholar]
  35. Santolaya RC, Bertini F. 1970. Z. Anat. Entwickl. Gesch. 131:148–55 [Google Scholar]
  36. Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H. 1993. EMBO J. 12:749–58 [Google Scholar]
  37. Hop C, Fontijn R, van Mourik JA, Pannekoek H. 1997. Exp. Cell Res. 230:352–61 [Google Scholar]
  38. Journet AM, Saffaripour S, Cramer EM, Tenza D, Wagner DD. 1993. Eur. J. Cell Biol. 60:31–41 [Google Scholar]
  39. McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. 1989. J. Clin. Invest. 84:92–99 [Google Scholar]
  40. Bonfanti R, Furie BC, Furie B, Wagner DD. 1989. Blood 73:1109–12 [Google Scholar]
  41. Vischer UM, Wagner DD. 1993. Blood 82:1184–91 [Google Scholar]
  42. Disdier M, Morrissey JH, Fugate RD, Bainton DF, McEver RP. 1992. Mol. Biol. Cell 3:309–21 [Google Scholar]
  43. Wagner DD. 1990. Annu. Rev. Cell Biol. 6:217–46 [Google Scholar]
  44. Vischer UM, Wollheim CB. 1997. Thromb. Haemost. 77:1182–88 [Google Scholar]
  45. Richardson M, Tinlin S, De Reske M, Webster S, Senis Y, Giles AR. 1994. Arterioscler. Thromb. 14:990–99 [Google Scholar]
  46. Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1977. Lancet 1:869–72 [Google Scholar]
  47. Moffat EH, Giddings JC, Bloom AL. 1984. Br. J. Haematol. 57:651–62 [Google Scholar]
  48. Booth F, Allington MJ, Cederholm-Williams SA. 1987. Br. J. Haematol. 67:71–78 [Google Scholar]
  49. Fowler WE, Fretto LJ, Hamilton KK, Erickson HP, McKee PA. 1985. J. Clin. Invest. 76:1491–500 [Google Scholar]
  50. Fretto LJ, Fowler WE, McCaslin DR, Erickson HP, McKee PA. 1986. J. Biol. Chem. 261:15679–89 [Google Scholar]
  51. Wagner DD, Fay PJ, Sporn LA, Sinha S, Lawrence SO, Marder VJ. 1987. Proc. Natl. Acad. Sci. USA 84:1955–59 [Google Scholar]
  52. Borchiellini A, Fijnvandraat K, ten Cate JW, Pajkrt D, van Deventer SJ. et al. 1996. Blood 88:2951–58 [Google Scholar]
  53. Takagi J, Kasahara K, Sekiya F, Inada Y, Saito Y. 1989. J. Biol. Chem. 264:10425–30 [Google Scholar]
  54. Isobe T, Hisaoka T, Shimizu A, Okuno M, Aimoto S. et al. 1997. J. Biol. Chem. 272:8447–53 [Google Scholar]
  55. Santoro SA. 1981. Thromb. Res. 21:689–91 [Google Scholar]
  56. Morton LF, Griffin B, Pepper DS, Barnes MJ. 1983. Thromb. Res. 32:545–56 [Google Scholar]
  57. Rand JH, Patel ND, Schwartz E, Zhou SL, Potter BJ. 1991. J. Clin. Invest. 88:253–59 [Google Scholar]
  58. Houdijk WP, Sakariassen KS, Nievelstein PF, Sixma JJ. 1985. J. Clin. Invest. 75:531–40 [Google Scholar]
  59. Wagner DD, Urban-Pickering M, Marder VJ. 1984. Proc. Natl. Acad. Sci. USA 81:471–75 [Google Scholar]
  60. de Groot PG, Ottenhof-Rovers M, van Mourik JA, Sixma JJ. 1988. J. Clin. Invest. 82:65–73 [Google Scholar]
  61. von der Mark H, Aumailley M, Wick G, Fleischmajer R, Timpl R. 1984. Eur. J. Biochem. 142:493–502 [Google Scholar]
  62. Colombatti A, Bonaldo P. 1987. J. Biol. Chem. 262:14461–66 [Google Scholar]
  63. Wu XX, Gordon RE, Glanville RW, Kuo HJ, Uson RR, Rand JH. 1996. Am. J. Pathol. 149:283–91 [Google Scholar]
  64. Ross JM, McIntire LV, Moake JL, Rand JH. 1995. Blood 85:1826–35 [Google Scholar]
  65. Roth GJ, Titani K, Hoyer LW, Hickey MJ. 1986. Biochemistry 25:8357–61 [Google Scholar]
  66. Kalafatis M, Takahashi Y, Girma JP, Meyer D. 1987. Blood 70:1577–83 [Google Scholar]
  67. Pareti FI, Niiya K, McPherson JM, Ruggeri ZM. 1987. J. Biol. Chem. 262:13835–41 [Google Scholar]
  68. Lankhof H, van Hoeij M, Schiphorst ME, Bracke M, Wu YP. et al. 1996. Thromb. Haemost. 75:950–58 [Google Scholar]
  69. Bienkowska J, Cruz M, Atiemo A, Handin R, Liddington R. 1997. J. Biol. Chem. 272:25162–67 [Google Scholar]
  70. Huizinga EG, van der Plas RM, Sixma JJ, Kroon J, Gros P. 1997. Structure 5:1147–56 [Google Scholar]
  71. Lee JO, Rieu P, Arnaout MA, Liddington R. 1995. Cell 80:631–38 [Google Scholar]
  72. Qu AD, Leahy DJ. 1995. Proc. Natl. Acad. Sci. USA 92:10277–81 [Google Scholar]
  73. Branden CI. 1980. Q. Rev. Biophys. 13:317–38 [Google Scholar]
  74. Du X, Beutler L, Ruan C, Castaldi PA, Berndt MC. 1987. Blood 69:1524–27 [Google Scholar]
  75. Modderman PW, Admiraal LG, Sonnenberg A, Borne AEGKV. 1992. J. Biol. Chem. 267:364–69 [Google Scholar]
  76. Marchese P, Murata M, Mazzucato M, Pradella P, De Marco L. et al. 1995. J. Biol. Chem. 270:9571–78 [Google Scholar]
  77. Scott JP, Montgomery RR, Retzinger GS. 1991. J. Biol. Chem. 266:8149–55 [Google Scholar]
  78. Berndt MC, Du X, Booth WJ. 1988. Biochemistry 27:633–40 [Google Scholar]
  79. Andrews RK, Booth WJ, Gorman JJ, Castaldi PA, Berndt MC. 1989. Biochemistry 28:8317–26 [Google Scholar]
  80. Matsushita T, Sadler JE. 1995. J. Biol. Chem. 270:13406–14 [Google Scholar]
  81. Kroner PA, Frey AB. 1996. Biochemistry 35:13460–68 [Google Scholar]
  82. Matsushita T, Sadler JE. 1997. Thromb. Haemost. Suppl.:364 [Google Scholar]
  83. Hillery CA, Mancuso DJ, Sadler JE, Ponder JW, Jozwiak ML. et al. 1998. Blood 91:1572–81 [Google Scholar]
  84. Andrews RK, Gorman JJ, Booth WJ, Corino GL, Castaldi PA, Berndt MC. 1989. Biochemistry 28:8326–36 [Google Scholar]
  85. Miura S, Fujimura Y, Sugimoto M, Kawasaki T, Ikeda Y. et al. 1994. Blood 84:1553–58 [Google Scholar]
  86. Zhang L, Plow EF. 1996. J. Biol. Chem. 271:29953–57 [Google Scholar]
  87. Celikel R, Varughese KI, Madhusudan, Yoshioka A, Ware J, Ruggeri ZM. 1997. Thromb. Haemost. Suppl.:769 [Google Scholar]
  88. Cruz MA, Emsley J, Diacovo T, Liddington R, Handin RI. 1997. Blood 90(Suppl. 1):430a [Google Scholar]
  89. Marguerie GA, Plow EF, Edgington TS. 1979. J. Biol. Chem. 254:5357–63 [Google Scholar]
  90. Plow EF, Ginsberg MH. 1981. J. Biol. Chem. 256:9477–82 [Google Scholar]
  91. Fujimoto T, Ohara S, Hawiger J. 1982. J. Clin. Invest. 69:1212–22 [Google Scholar]
  92. Savage B, Saldivar E, Ruggeri ZM. 1996. Cell 84:289–97 [Google Scholar]
  93. Fressinaud E, Baruch D, Girma JP, Sakariassen KS, Baumgartner HR, Meyer D. 1988. J. Lab. Clin. Med. 112:58–67 [Google Scholar]
  94. Fressinaud E, Girma J-P, Sadler JE, Baumgartner HR, Meyer D. 1990. Thromb. Haemost. 64:589–93 [Google Scholar]
  95. Ruggeri ZM. 1997. J. Clin. Invest. 99:559–64 [Google Scholar]
  96. Back LD, Radbill JR, Crawford DW. 1977. J. Biomech. 10:339–53 [Google Scholar]
  97. Konstantopoulos K, McIntire LV. 1996. J. Clin. Invest. 98:2661–65 [Google Scholar]
  98. Siedlecki CA, Lestini BJ, Kottke-Marchant KK, Eppell SJ, Wilson DL, Marchant RE. 1996. Blood 88:2939–50 [Google Scholar]
  99. Sadler JE, Davie EW. 1994. In The Molecular Basis of Blood Diseases, ed. G Stamatoyannopoulos, AW Nienhuis, PW Majerus, H Varmus 657–700 Philadelphia: WB Saunders
  100. Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ. 1995. Blood 85:3150–57 [Google Scholar]
  101. Vlot AJ, Koppelman SJ, Meijers JCM, Damas C, van den Berg HM. et al. 1996. Blood 87:1809–16 [Google Scholar]
  102. Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS. 1987. J. Biol. Chem. 262:8443–46 [Google Scholar]
  103. Lollar P, Hill-Eubanks DC, Parker CG. 1988. J. Biol. Chem. 263:10451–55 [Google Scholar]
  104. Leyte A, van Schijndel HB, Niehrs C, Huttner WB, Verbeet MP. et al. 1991. J. Biol. Chem. 266:740–46 [Google Scholar]
  105. Fujimura Y, Titani K, Holland LZ, Roberts JR, Kostel P. et al. 1987. J. Biol. Chem. 262:1734–39 [Google Scholar]
  106. Sobel M, McNeill PM, Carlson PL, Kermode JC, Adelman B. et al. 1991. J. Clin. Invest. 87:1787–93 [Google Scholar]
  107. Christophe O, Obert B, Meyer D, Girma JP. 1991. Blood 78:2310–17 [Google Scholar]
  108. Sixma JJ, Schiphorst ME, Verweij CL, Pannekoek H. 1991. Eur. J. Biochem. 196:369–75 [Google Scholar]
  109. Ginsburg D, Handin RI, Bonthron DT, Donlon TA, Bruns GAP. et al. 1985. Science 228:1401–6 [Google Scholar]
  110. Kuwano A, Morimoto Y, Nagai T, Fukushima Y, Ohashi H. et al. 1996. Hum. Genet. 97:95–98 [Google Scholar]
  111. Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB. et al. 1989. J. Biol. Chem. 264:19514–27 [Google Scholar]
  112. Porter CA, Goodman M, Stanhope MJ. 1996. Mol. Phylogenet. Evol. 5:89–101 [Google Scholar]
  113. Springer MS, Cleven GC, Madsen O, de Jong WW, Waddell VG. et al. 1997. Nature 388:61–64 [Google Scholar]
  114. Patracchini P, Calzolari E, Aiello V, Palazzi P, Banin P. et al. 1989. Hum. Genet. 83:264–66 [Google Scholar]
  115. Mancuso DJ, Tuley EA, Westfield LA, Lester-Mancuso TL, Le Beau MM. et al. 1991. Biochemistry 30:253–69 [Google Scholar]
  116. Eikenboom JCJ, Vink T, Briët E, Sixma JJ, Reitsma PH. 1994. Proc. Natl. Acad. Sci. USA 91:2221–24 [Google Scholar]
  117. Colombatti A, Bonaldo P. 1991. Blood 77:2305–15 [Google Scholar]
  118. Perkins SJ, Smith KF, Williams SC, Haris PI, Chapman D, Sim RB. 1994. J. Mol. Biol. 238:104–19 [Google Scholar]
  119. Shaw SK, Cepek KL, Murphy EA, Russell GJ, Brenner MB, Parker CM. 1994. J. Biol. Chem. 269:6016–25 [Google Scholar]
  120. Van der Vieren M, Le Trong H, Wood CL, Moore PF, St. John T. et al. 1995. Immunity 3:683–90 [Google Scholar]
  121. Deák F, Piecha D, Bachrati C, Paulsson M, Kiss I. 1997. J. Biol. Chem. 272:9268–74 [Google Scholar]
  122. Wagener R, Kobbe B, Paulsson M. 1997. FEBS Lett. 413:129–34 [Google Scholar]
  123. Toribara NW, Ho SB, Gum E, Gum JR Jr, Lau P, Kim YS. 1997. J. Biol. Chem. 272:16398–403 [Google Scholar]
  124. Perez-Vilar J, Eckhardt AE, Hill RL. 1996. J. Biol. Chem. 271:9845–50 [Google Scholar]
  125. Hardy DM, Garbers DL. 1995. J. Biol. Chem. 270:26025–28 [Google Scholar]
  126. Tomley FM, Clarke LE, Kawazoe U, Dijkema R, Kok JJ. 1991. Mol. Biochem. Parasitol. 49:277–88 [Google Scholar]
  127. Wilson R, Ainscough R, Anderson K, Baynes C, Berks M. et al. 1994. Nature 368:32–38 [Google Scholar]
  128. Trottein F, Triglia T, Cowman AF. 1995. Mol. Biochem. Parasitol. 74:129–41 [Google Scholar]
  129. Kotani E, Yamakawa M, Iwamoto S, Tashiro M, Mori H. et al. 1995. Biochim. Biophys. Acta 1260:245–58 [Google Scholar]
  130. Holmberg L, Nilsson IM. 1992. Eur. J. Haematol. 48:127–41 [Google Scholar]
  131. Rodeghiero F, Castaman G, Dini E. 1987. Blood 69:454–59 [Google Scholar]
  132. Sadler JE. 1994. Thromb. Haemost. 71:520–25 [Google Scholar]
  133. Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. 1987. Blood 69:1691–95 [Google Scholar]
  134. Eikenboom JC, Reitsma PH, Peerlinck KMJ, Briët E. 1993. Lancet 341:982–86 [Google Scholar]
  135. Eikenboom JCJ, Reitsma PH, Matsushita T, Tuley EA, Castaman G. et al. 1996. Blood 88:2433–41 [Google Scholar]
  136. Ginsburg D, Sadler JE. 1993. Thromb. Haemost. 69:177–84 [Google Scholar]
  137. Lyons SE, Bruck ME, Bowie EJW, Ginsburg D. 1992. J. Biol. Chem. 267:4424–30 [Google Scholar]
  138. Gaucher C, Diéval J, Mazurier C. 1994. Blood 84:1024–30 [Google Scholar]
  139. Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. 1980. N. Engl. J. Med. 302:1047–51 [Google Scholar]
  140. Holmberg L, Dent JA, Schneppenheim R, Budde U, Ware J, Ruggeri ZM. 1993. J. Clin. Invest. 91:2169–77 [Google Scholar]
  141. Ribba AS, Christophe O, Derlon A, Cherel G, Siguret V. et al. 1994. Blood 83:833–41 [Google Scholar]
  142. Nishino M, Girma J-P, Rothschild C, Fressinaud E, Meyer D. 1989. Blood 74:1591–99 [Google Scholar]
  143. Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. 1990. Blood 75:20–26 [Google Scholar]
  144. Mazurier C. 1992. Thromb. Haemost. 67:391–96 [Google Scholar]
  145. Mazurier C, Meyer D. 1996. Thromb. Haemost. 76:270–74 [Google Scholar]
  146. Schneppenheim R, Budde U, Krey S, Drewke E, Bergmann F. et al. 1996. Thromb. Haemost. 76:598–602 [Google Scholar]
  147. Zhang ZP, Blombäck M, Nyman D, Anvret M. 1993. Proc. Natl. Acad. Sci. USA 90:7937–40 [Google Scholar]
  148. Zhang ZP, Lindstedt M, Falk G, Blombäck M, Egberg N, Anvret M. 1992. Am. J. Hum. Genet. 51:850–58 [Google Scholar]
  149. Zhang ZP, Blombäck M, Egberg N, Falk G, Anvret M. 1994. Genomics 21:188–93 [Google Scholar]
  150. Schneppenheim R, Krey S, Bergmann F, Bock D, Budde U. et al. 1994. Hum. Genet. 94:640–52 [Google Scholar]
  151. Mannucci PM, Bloom AL, Larrieu MJ, Nilsson IM, West RR. 1984. Br. J. Haematol. 57:163–69 [Google Scholar]
  152. Weiss HJ, Ball AP, Mannucci PM. 1982. N. Engl. J. Med. 307:127 [Google Scholar]
  153. Beckmann G, Bork P. 1993. Trends Biochem. Sci. 18:40–41 [Google Scholar]
  154. Sadler JE. 1994. In Haemostasis and Thrombosis, ed. AL Bloom, CD Forbes, DP Thomas, EGD Tuddenham 843–57 Edinburgh: Churchill-Livingstone
/content/journals/10.1146/annurev.biochem.67.1.395
Loading
BIOCHEMISTRY AND GENETICS OF VON WILLEBRAND FACTOR
Annual Review of Biochemistry 67, 395 (1998); https://doi.org/10.1146/annurev.biochem.67.1.395
/content/journals/10.1146/annurev.biochem.67.1.395
/content/journals/10.1146/annurev.biochem.67.1.395
Loading

Data & Media loading...

  • Article Type: Introduction

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
  NODES
admin 1
Note 1