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I222 crystal form of despentapeptide (B26-B30) insulin provides new insights into the properties of monomeric insulin.

Whittingham JL, Youshang Z, Záková L, Dodson EJ, Turkenburg JP, Brange J, Dodson GG
Acta Crystallogr D Biol Crystallogr 62 505-11 (2006)
Cited: 2 times
EuropePMC logo PMID: 16627943

Abstract

Despentapeptide (des-B26-B30) insulin (DPI), an active modified insulin, has been crystallized in the presence of 20% acetic acid pH 2. A crystal structure analysis to 1.8 A spacing (space group I222) revealed that the DPI molecule, which is unable to make beta-strand interactions for physiological dimer formation and is apparently monomeric in solution, formed an alternative lattice-generated dimer. The formation of this dimer involved interactions between surfaces which included the B9-B19 alpha-helices (usually buried by the dimer-dimer contacts within the native hexamer). The two crystallographically independent molecules within the dimer were essentially identical and were similar in conformation to T-state insulin as seen in the T(6) insulin hexamer. An unusual feature of each molecule in the dimer was the presence of two independent conformations at the B-chain C-terminus (residues B20-B25). Both conformations were different from that of native insulin, involving a 3.5 A displacement of the B20-B23 beta-turn and a repositioning of residue PheB25 such that it made close van der Waals contact with the main body of the molecule, appearing to stabilize the B-chain C-terminus.

Articles citing this publication (2)

  1. Role of Proinsulin Self-Association in Mutant INS Gene-Induced Diabetes of Youth. Sun J, Xiong Y, Li X, Haataja L, Chen W, Mir SA, Lv L, Madley R, Larkin D, Anjum A, Dhayalan B, Rege N, Wickramasinghe NP, Weiss MA, Itkin-Ansari P, Kaufman RJ, Ostrov DA, Arvan P, Liu M. Diabetes 69 954-964 (2020)
  2. Biochemical contacts and collaborations between China and the U.K. since 1911. Dodson GG. Biochem. Soc. Trans. 39 1313-1322 (2011)


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