Molecular conformation of ubiquitinated structures and the implications for regulatory function.
The molecular conformation of ubiquitinated structures and the validity of the N-end rule were examined by simulating the molecular mechanics to ascertain the global energy-minimized structure. We examined the chemical linkage involved in attaching the ubiquitin carboxyl terminus to the N-terminus of three different x-hexapeptides, where x is the amino group of the acceptor peptide--either valine, arginine or glutamic acid--(x-K linkage) and to the epsilon-amino group of lysine of the acceptor hexapeptide x-glu1-his2-lys3-gly4-lys5-val6 (K-K linkage) through the formation of an isopeptide bond. Changes in conformation and molecular stability of the multi-ubiquitinated structures were determined by energy-minimization procedures using the SYBYL program developed by Tripos Associates. In the x-K linkage, the ubiquitin molecule is stretched in the beta-pleated sheets and beta-turns while the alpha-helices expand, as the molecule continues to unfold linearly. In the K-K linkage, the ubiquitin molecules have turned into a u-shaped, semi-circular alignment, contracting into a compact, folded structure.
Chun
P W
PW
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville 32610.
Jou
W S
WS
D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014452:Ubiquitins / Q000737:chemistry*
D014452:Ubiquitins