Spelling protein structure.

Area of Science:

• Structural Biology
• Protein Evolution
• Bioinformatics

Background:

• Analysis of prokaryotic proteomes suggests early proteins were small (25-35 amino acids).
• Protein crystal data supports the existence of universal closed loop structures in globular proteins of this size.

Purpose of the Study:

• To derive and structurally characterize sequence/structure prototypes representing early protein units.
• To develop a method for presenting proteins as assemblies of these ancestral prototype elements.
• To establish basic principles for sequence/structure prototype spelling of globular proteins.

Main Methods:

• Sequence analysis of complete prokaryotic proteomes.
• Protein crystallography to determine structural data.
• Derivation and structural characterization of sequence/structure prototypes.
• Analysis of the ATP-binding subunit of histidine permease for prototype element identification.

Main Results:

• Identified and characterized several sequence/structure prototypes, appearing as closed loops stabilized by van der Waals interactions.
• Prototypes exhibit conserved size but diverse secondary structures.
• Demonstrated that proteins can be represented as assemblies of modified prototype descendants, exemplified by the histidine permease subunit.

Conclusions:

• Early proteins likely originated from small, closed-loop structural units (prototypes).
• A novel 'prototype spelling' system can describe the sequence and structure of globular proteins.
• This framework provides fundamental principles for understanding protein assembly and evolution.