The structure and function of insulin: decoding the TR transition.

ABSTRACT: Crystal structures of insulin are remarkable for a long-range reorganization among three families of hexamers (designated T(6), T(3)R(3)(f), and R(6)). Although these structures are well characterized at atomic resolution, the biological implications of the TR transition remain the subject of speculation. Recent studies indicate that such allostery reflects a structural switch between distinct folding-competent and active conformations. Stereospecific modulation of this switch by corresponding d- and l-amino-acid substitutions yields reciprocal effects on protein stability and receptor-binding activity. Naturally occurring human mutations at the site of conformational change impair the folding of proinsulin and cause permanent neonatal-onset diabetes mellitus. The repertoire of classical s

SUBMITTER: Weiss MA 

PROVIDER: S-EPMC3297421 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature