Induced Fit in Protein Multimerization: The HFBI Case.
Hydrophobins, produced by filamentous fungi, are small amphipathic proteins whose biological functions rely on their unique surface-activity properties. Understanding the mechanistic details of the multimerization process is of primary importance to clarify the interfacial activity of hydrophobins. We used free energy calculations to study the role of a flexible β-hairpin in the multimerization process in hydrophobin II from Trichoderma reesei (HFBI). We characterized how the displacement of this β-hairpin controls the stability of the monomers/dimers/tetramers in solution. The regulation of the oligomerization equilibrium of HFBI will necessarily affect its interfacial properties, fundamental for its biological function and for technological applications. Moreover, we propose possible routes for the multimerization process of HFBI in solution. This is the first case where a mechanism by which a flexible loop flanking a rigid patch controls the protein-protein binding equilibrium, already known for proteins with charged binding hot-spots, is described within a hydrophobic patch.
Laboratory of Molecular Modeling and Drug Discovery, Istituto Italiano di Tecnologia, Genoa, Italy.
Laura
L
Riccardi
Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Pisa, Italy.
Paolo
http://orcid.org/0000-0001-6012-592X
P
Mereghetti
D001665:Binding Sites; D003198:Computer Simulation; D005656:Fungal Proteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D013499:Surface Properties; D014242:Trichoderma / Q000737:chemistry*
D005656:Fungal Proteins