Sialidase-like Asp-boxes: sequence-similar structures within different protein folds

Area of Science:

• Biochemistry
• Structural Biology
• Evolutionary Biology

Background:

• Protein homology is commonly inferred from sequence similarity, typically across entire protein domains.
• Conserved sequence motifs are crucial for understanding protein function and evolution.
• Asp box motifs were previously identified in sialidases and neuraminidases.

Purpose of the Study:

• To identify and characterize Asp box motifs in novel sequence and structural contexts.
• To explore the prevalence and evolutionary significance of Asp boxes across different protein families.
• To investigate potential shared functions and evolutionary origins of proteins containing Asp boxes.

Main Methods:

• Combined sequence and structure-based analyses were employed.
• Bioinformatic searches were conducted to identify Asp box occurrences.
• Comparative analysis of protein structures and sequences was performed.

Main Results:

• Asp box motifs were identified in new structural and sequence contexts, often within beta hairpins.
• These motifs were detected in over nine diverse protein families, including ribonucleases, sulfite oxidases, reelin, netrins, lipoprotein receptors, and glycosyl hydrolases.
• Proteins containing Asp boxes exhibited significant sequence and three-dimensional structure differences outside the motif.

Conclusions:

• Asp box motifs represent a conserved structural and sequence feature linking evolutionarily distant proteins.
• The presence of Asp boxes suggests a broader definition of homology than solely relying on overall sequence similarity.
• Further research is needed to elucidate the functional roles and evolutionary trajectories of Asp-box containing proteins.