Amino acid homorepeats in tape measure proteins correlate with bacteriophage tail length

Abstract

The tape measure protein (TMP) dictates the tail length of tailed bacteriophages. However, the sequence features that drive the process of length fine- tuning have not yet been described. Tandem repeats (TRs), stretches of aas organized as multiple adjacent copies of the same or very similar sequence motif, are contributors to TMP length variation. Homorepeats (polyX regions) are a specific type of TRs composed of stretches of identical aas, forming low- complexity regions that contribute to protein structural flexibility and dynamics. Here, we performed a large- scale analysis of polyX regions across 12 million phage proteins to test whether these homorepeats help explain the variable length of flexible phage tails. PolyX tracts were detected in 41% of all phage proteins and in 95.5% of TMPs, with polyA, polyG, polyS and polyT dominating the composition. Furthermore, the number of polyX tracts in TMPs scaled directly with protein length. About half of the TMPs have both polyX and TRs (23,469 out of 45,500 TMPs), but nearly half of the polyX- containing TMPs lacked any TRs (19,999 out of 43,468 TMPs), showing that polyX are independent features rather than by- products of larger repeats. Morphological comparisons showed that phages with long and flexible tails (Siphovirus morphotype) combine polyX and TRs, whereas shorter or contractile- tailed phages rely mostly on polyX. Last, the total aa content in polyX regions correlated significantly with experimentally measured tail lengths (R²=0.811, P=1.56×10−⁴). Our results identify polyX tracts as an important and tunable component of TMPs that enable precise control of phage tail length.