Structural changes and facilitated association of tropoelastin.
Circular dichroism studies of tropoelastin secondary structure show 4+/-1% alpha-helix in aqueous solutions. This is in contrast to the substantially higher amounts (up to 23+/-7%) of alpha-helix predicted by computer algorithms, which propose that regions of alpha-helix are limited to the alanine-rich cross-linking domains. Through the addition of trifluoroethanol, the amount of alpha-helix increased to 17+/-1%, equivalent to that expected on the basis of primary structure. The physiological ability of the protein to coacervate and the critical concentration of monomer required for coacervation were unaffected by levels of alpha-helix. However, the temperature required for coacervation decreased linearly with increasing alpha-helical structure, which correlates with the participation of alpha-helices in association. We propose that the alanine-rich cross-linking domains exist as nascent helices in tropoelastin in aqueous solution. We further suggest a novel mechanism for coacervation whereby formation of alpha-helices and subsequent helical side chain interactions limit the conformational flexibility of the polypeptide, to facilitate associations between hydrophobic domains during elastogenesis.
Muiznieks
Lisa D
LD
School of Molecular and Microbial Biosciences G08, University of Sydney, Sydney, New South Wales 2006, Australia.
Jensen
Sacha A
SA
Weiss
Anthony S
AS
D000409:Alanine / Q000737:chemistry; D000465:Algorithms; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D012984:Software; D013053:Spectrophotometry; D013696:Temperature; D014333:Tropoelastin / Q000737:chemistry* / Q000378:metabolism*; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
D010455:Peptides; D014333:Tropoelastin; D014867:Water; D000409:Alanine