Abstract:
:The crystal structure of insulin has been investigated in a variety of dimeric and hexameric assemblies. Interest in dynamics has been stimulated by conformational variability among crystal forms and evidence suggesting that the functional monomer undergoes a conformational change on receptor binding. Here, we employ Raman spectroscopy and Raman microscopy to investigate well-defined oligomeric species: monomeric and dimeric analogs in solution, native T(6) and R(6) hexamers in solution and corresponding polycrystalline samples. Remarkably, linewidths of Raman bands associated with the polypeptide backbone (amide I) exhibit progressive narrowing with successive self-assembly. Whereas dimerization damps fluctuations at an intermolecular beta-sheet, deconvolution of the amide I band indicates that formation of hexamers stabilizes both helical and non-helical elements. Although the structure of a monomer in solution resembles a crystallographic protomer, its encagement in a native assembly damps main-chain fluctuations. Further narrowing of a beta-sheet-specific amide I band is observed on reorganization of insulin in a cross-beta fibril. Enhanced flexibility of the native insulin monomer is in accord with molecular dynamics simulations. Such conformational fluctuations may initiate formation of an amyloidogenic nucleus and enable induced fit on receptor binding.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Dong J,Wan Z,Popov M,Carey PR,Weiss MAdoi
10.1016/s0022-2836(03)00536-9keywords:
subject
Has Abstractpub_date
2003-07-04 00:00:00pages
431-42issue
2eissn
0022-2836issn
1089-8638pii
S0022283603005369journal_volume
330pub_type
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