Protoglobin is the first globin found in Archaea. Its biological role is still unknown, although this protein can bind O(2), CO, and NO reversibly in vitro. The X-ray structure of Methanosarcina acetivorans protoglobin (MaPgb) has shown that access of ligands to the heme, which is completely buried within the protein matrix, can be granted by two apolar tunnels, which are mainly defined by helices G and B (tunnel 1), and helices B and E (tunnel 2). Here we analyze the structural and dynamical behavior of MaPgb through molecular dynamics and computational techniques aimed at shedding light on distinctive features of ligand migration through the tunnels that may be linked to functionality. While tunnel 2 is found to be accessible to diatomic ligands in both deoxygenated and oxygenated forms of the protein, the accessibility of tunnel 1 is controlled through the synergistic effect of both the protein dimeric state and the presence of the heme-bound ligand. Thus, dimerization mainly affects the spatial arrangement of helix G, which influences the shape of tunnel 1. Ligand accessibility through this tunnel is regulated by Phe(145)G8, which can adopt open and closed conformations. Noteworthy, the ratio between open and closed states is modulated by protein dimerization and more strikingly by ligand binding. In particular, sensing of the ligand is mediated by Phe(93)E11, and the steric hindrance between Phe(93)E11 and the hemebound ligand alters the structural and dynamical behavior of helices B and E, which facilitates opening of tunnel 1. This functional mechanism provides a basis to understand the finding that ligation favors fast rebinding from ligand binding kinetic to MaPgb. Finally, it also suggests that MaPgb might be physiologically involved in a ligand-controlled bimolecular chemical process.