A protein three-dimensional structure is essentially determined by its amino acid sequence, and thus by the information contained therein. Although "protein folders" have long studied what physical forces are important to stabilize a protein structure, it is only recently that one has experimentally asked the question: how much and what information is prerequisite for stabilizing a protein structure. Here, we describe two recent experiments in which the information contents of two protein sequences have been dramatically decreased and nevertheless the proteins remain active and natively structured. We discuss the implication of these findings both from a protein structure and a molecular evolution point of view.
The N-terminal FERM domain of ERM (ezrin/radixin/moesin) proteins is responsible for membrane binding by interaction with phosphatidylinositol 4,5-bisphosphate (PIP2) and the adhesion proteins such as ICAMs. We have determined the crystal structures of the mouse radixin FERM domain, and its complexes with inositol-(1,4,5)-trisphosphate (IP3), which is a head group of PIP2, and with the ICAM-2 cytosolic tail. IP3 binds to a basic cleft between subdomains A and C, which is a different site from those found in PH domains. The ICAM-2 peptide binds to the subdomain C mediated by a β-β association and several side-chain interactions.
The RepE initiator protein of F plasmid plays an essential role in initiating DNA replication in mini-F origin. RepE exhibits two major functions; the RepE monomer plays as a replication initiator which binds to direct repeats (iterons) in origin, while the RepE dimer as an autogenous repressor to the repE operator. The crystal structure of RepE monomer (RepE54) as a complex with an iteron DNA was determined as the first 3-D structure for procaryotic initiator proteins. The RepE monomer consists of topologically similar N- and C-terminal domains related by an internal pseudo two-fold symmetry, which has not been expected from its amino acid sequence. Both domains bind to two major grooves of iteron (19bp) with different binding affinities. The C-terminal domain plays the leading role in this binding, while the N-terminal domain has the additional role in dimerization.