Single-walled tubulin ring polymers.
An unusual class of nanoscopic, ring-shaped, single-walled biopolymers arises when alphabeta-tubulin is mixed with certain small peptides obtained from various marine organisms and cyanobacteria. The single-ring structures, whose mean molecular weight depends on the specific peptide added to the reaction mixture, usually have sharp mass distributions corresponding, e.g., to rings containing eight tubulin dimers (when the added peptide is cryptophycin) and 14 dimers (e.g., with dolastatin). Although the ring-forming peptides have been shown to possess antimitotic properties when tested with cultured eukaryotic cells (and thus have generated considerable interest as possible agents to be used in the treatment of cancer), it is not our intention to extensively discuss the potential pharmacological properties of the peptides. Rather, we will review the polymeric structures that form and illustrate how certain physical techniques can be used to characterize their properties and interactions. The nanoscopic size and particular geometry of the individual rings make them appropriate targets for scattering and hydrodynamic techniques that provide details about their structure in solution, but it is necessary to relate measured data to postulated structures by nontrivial, albeit straight-forward, mathematical, and computational means. We will discuss how this is done when one uses such methods as small angle neutron scattering, dynamic light scattering, fluorescence correlation spectroscopy, and sedimentation velocity measurements. Moreover, we show that, by using several techniques, one can eliminate degeneracy to provide better discrimination between model structures.
Boukari
Hacène
H
Laboratory of Integrative and Medical Biophysics, NICHD, National Institutes of Health, Bethesda, MD 20892, USA. boukarih@mail.nih.gov
Sackett
Dan L
DL
Schuck
Peter
P
Nossal
Ralph J
RJ
D000818:Animals; D001704:Biopolymers / Q000737:chemistry; D002417:Cattle; D020285:Cryoelectron Microscopy; D047630:Depsipeptides / Q000737:chemistry; D066298:In Vitro Techniques; D008027:Light; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D033363:Neutron Diffraction; D051381:Rats; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D014404:Tubulin / Q000737:chemistry* / Q000648:ultrastructure
D001704:Biopolymers; D047630:Depsipeptides; D046912:Multiprotein Complexes; D014404:Tubulin; C064570:dolastatin 10; C510034:cryptophycin 1