A strong correlation between consensus sequences and unique super secondary structures in leucine rich repeats

Area of Science:

• Structural Biology
• Protein Science
• Bioinformatics

Background:

• Leucine-rich repeats (LRRs) are prevalent protein motifs found across all domains of life.
• LRRs consist of tandem repeats, typically 20-30 residues long, forming solenoid structures through parallel beta-strand stacking.
• Specific LRR classes, including Plant-specific, Leptospira-like, and SDS22-like, exhibit distinct lengths and incorporate 3(10)-helices.

Purpose of the Study:

• To investigate the sequence-structure correlations within LRR proteins.
• To elucidate the super secondary structures adopted by LRR domains.
• To identify key sequence motifs and structural parameters governing LRR solenoid formation.

Main Methods:

• Utilized secondary structure assignment and HELFIT analysis on atomic coordinates from 43 LRR protein crystal structures.
• Calculated helix axis, pitch, radius, residues per turn, and handedness using HELFIT.
• Defined three structural parameters based on helix axes of 3(10)-helix, beta-turn, and LRR-domain.

Main Results:

• LRR structures consistently exhibit super secondary structures composed of a 3(10)-helix and one or two Type I beta-turns.
• A conserved LxxLxxL sequence motif (Leu, Ile, Val, Phe, or Cys) is identified as a critical determinant for these super secondary structures.
• One proposed structural parameter acts as a geometrical invariant for LRR solenoid structures.

Conclusions:

• The study reveals a conserved super secondary structure in LRR domains, comprising 3(10)-helices and beta-turns.
• The LxxLxxL sequence motif plays a vital role in mediating medium-range interactions essential for LRR super secondary structure formation.
• A novel geometrical invariant parameter is proposed for characterizing LRR solenoid structures.