Autonomous Sequences in Myoglobin Emerging from X-ray Structure of Holomyoglobin.

The proposed continuous folding structure units are fundamental to analyze protein structure. Here, we could elucidate for the first time two types of hydrophobic core networks in apomyoglobin using continuous folding structure units. In myoglobin, two autonomous sequences emerged clearly. We could thus characterize the autonomous sequences using well-defined hydrophobic core networks within respective semifolds. A hydrophobic core is defined as a pair of topology-local hydrophobic amino acids in different folding structures. Hydrophobic core formation is indispensable to stabilize the different folding structures via an efficient hydrophobic interaction. Autonomous sequences in myoglobin encode tertiary structure information for semifolds. These sequences fold autonomously into small sets of continuous folding structure units to grow separate semifolds on each separate framework. The autonomous sequence can be defined as the local sequence assigned to the small set of continuous folding structure units. They create the discrete hydrophobic region in a semifold by assembly of their hydrophobic regions. Semifolds were characterized by discrete hydrophobic regions stabilized by respective type I hydrophobic core networks, which were present within each semifold. The discrete hydrophobic region of a semifold propagated itself with that of a different semifold by hydrophobic interactions in type II hydrophobic core network, which was present between different semifolds, as observed by the X-ray structures of semifolds. The most significant feature of semifolds in apomyoglobin was that they could be verified by the X-ray structure of holomyoglobin regardless of the instability of folds characteristic to autonomous sequence fragments. This work presents the first description of autonomous sequences.

Protein Folding Structures: Formation of Folding Structures Based on Probability Theory.

To the best of our knowledge, this is the first study that shows that the X-ray structures of proteins can be dissected into their continuous folding structure units. Each folding structure unit was designed such that both the terminal di- or tri-peptide sequences shared common sequences with the two adjacent folding structure units. To encode the folding structure information of proteins into their amino acid sequences, we proposed 44 kinds of folding elements, which covered all of the amino acids in the protein chains, and defined all folding structure units. The folding element was defined to mean a minimum structural piece, which covered the frame of the main chain of each amino acid in a protein chain. A folding structure unit of a local sequence could be fully characterized by the sequential combination of individual folding elements assigned to each amino acid. The folding structure information showed amino acid preferences in various positions in folding structure units. Folding structure formation proceeded on the basis of probability theory. Strikingly, relative formation ability analysis clearly indicated that we can decode the types and the chain length of folding structure units from the amino acid sequence of a protein.