title: Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin.
abstract: Proteins harbor a number of cavities of relatively small volume. Although these packing defects are associated with the thermodynamic instability of the proteins, the cavities also play specific roles in controlling protein functions, e.g., ligand migration and binding. This issue has been extensively studied in a well-known protein, myoglobin (Mb). Mb reversibly binds gas ligands at the heme site buried in the protein matrix and possesses several internal cavities in which ligand molecules can reside. It is still an open question as to how a ligand finds its migration pathways between the internal cavities. Here, we report on the dynamic and sequential structural deformation of internal cavities during the ligand migration process in Mb. Our method, the continuous illumination of native carbonmonoxy Mb crystals with pulsed laser at cryogenic temperatures, has revealed that the migration of the CO molecule into each cavity induces structural changes of the amino acid residues around the cavity, which results in the expansion of the cavity with a breathing motion. The sequential motion of the ligand and the cavity suggests a self-opening mechanism of the ligand migration channel arising by induced fit, which is further supported by computational geometry analysis by the Delaunay tessellation method. This result suggests a crucial role of the breathing motion of internal cavities as a general mechanism of ligand migration in a protein matrix.
authors.affiliation: Department of Materials Science, Tokyo Institute of Technology, Meguro, Tokyo 152-8551, Japan.
authors.forename: Ayana
authors.initials: A
authors.lastname: Tomita
authors.forename: Tokushi
authors.initials: T
authors.lastname: Sato
authors.forename: Kouhei
authors.initials: K
authors.lastname: Ichiyanagi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nozawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Matthieu
authors.initials: M
authors.lastname: Chollet
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Kawai
authors.forename: Sam-Yong
authors.initials: SY
authors.lastname: Park
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuduki
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamato
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Koshihara
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Adachi
mesh_terms: D018360:Crystallography, X-Ray; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism; D010777:Photochemistry
chemical_list: D008024:Ligands; D009211:Myoglobin