Role of loop-helix interactions in stabilizing four-helix bundle proteins.
One of the critical issues regarding proteins with a four-helix bundle motif is which interactions play the major role in stabilizing this type of folded structure: the interaction among the four alpha-helices or the interaction between the loop and helix segments. To answer this question, an energetic analysis has been carried out for three proteins with a four-helix bundle--namely, methemerythrin, cytochrome b-562, and cytochrome c'. The structures on which the analysis has been made were derived from their respective crystallographic coordinates. All three proteins have long helices (16-26 residues) and most of their loops are short (3-5 residues). However, it was found in all three proteins that loop-helix interactions were stronger than helix-helix interactions. Moreover, not only the nonbonded component but also the electrostatic component of the interaction energy were dominated by loop-helix interactions rather than by interhelix interactions, although the latter involve favorable helix-dipole interactions due to the antiparallel arrangement of neighboring helices. The results of the energetic analysis indicate that the loop segments, whether they are in a theoretical model or in real proteins, play a significant role in stabilizing proteins with four-helix bundles.
Chou
K C
KC
Computational Chemistry, Upjohn Laboratories, Kalamazoo, MI 49001.
Maggiora
G M
GM
Scheraga
H A
HA
D003573:Cytochrome b Group / Q000737:chemistry*; D003574:Cytochrome c Group / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006422:Hemerythrin / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D013816:Thermodynamics; D014961:X-Ray Diffraction
D003573:Cytochrome b Group; D003574:Cytochrome c Group; D029968:Escherichia coli Proteins; D006422:Hemerythrin; C019004:methemerythrin; C017850:cytochrome b562, E coli