HETERODIMER FORMATION AND CRYSTAL NUCLEATION OF GRAMICIDIN-D

The linear pentadecapeptide antibiotic gramicidin D is a heterogeneous mixture of six components. Precise refinements of three-dimensional s tructures of naturally occurring gramicidin D in crystals obtained fro m methanol, ethanol, and n-propanol demonstrate the unexpected presenc e of stable left-handed antiparallel double-helical heterodimers that vary with the crystallization solvent. The side chains of Trp residues in the three structures exhibit sequence-specific patterns of conform ational preference. Tyr substitution for Trp at position 11 appears to favor beta ribbon formation and stabilization of the antiparallel dou ble helix that acts as a template for gramicidin folding and nucleatio n of different crystal forms. The fact that a minor component in a het erogeneous mixture influences aggregation and crystal nucleation has p otential applications to other systems in which anomalous behavior is exhibited by aggregation of apparently homogeneous materials, such as the enigmatic behavior of prion proteins.