Adaptive amino acid replacements accompanied by domain fusion in reverse transcriptase

Area of Science:

• Protein evolution
• Molecular biology
• Biochemistry

Background:

• Protein evolution involves amino acid replacement and reorganization of structural/functional units.
• Multidomain proteins, like reverse transcriptase (RT), likely evolved through fusion of smaller domains.
• RT comprises a polymerase domain and a ribonuclease H (RNase H) domain.

Purpose of the Study:

• To analyze amino acid replacement patterns in free RNase H (RNase HI) and integrated RNase H domains within RT.
• To compare these patterns and understand the evolutionary implications of domain fusion.
• To investigate adaptive amino acid substitutions at interdomain interfaces.

Main Methods:

• Comparative analysis of amino acid residue site patterns.
• Examination of free-form RNase HI and integrated RNase H domains in RT.
• Identification of residue sites involved in interdomain contacts.

Main Results:

• Significant amino acid replacements were observed at four of 29 interdomain contact sites.
• Hydrophilic residues in free RNase HI were replaced by hydrophobic/ambivalent ones in the integrated RNase H domain of RT.
• These substitutions enhance interdomain stability through hydrophobic interactions.

Conclusions:

• Domain fusion in protein evolution can be facilitated by a limited number of adaptive amino acid substitutions.
• Hydrophobic interactions at domain interfaces play a crucial role in stabilizing fused protein structures.
• This study provides insights into the evolutionary mechanisms of multidomain proteins.