| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-155 |
Sentence |
denotes |
New structural and functional aspects of the type I interferon-receptor interaction revealed by comprehensive mutational analysis of the binding interface. |
| T2 |
156-373 |
Sentence |
denotes |
Type I interferons bind to two cell surface receptors, ifnar1 and ifnar2, as the first step in the activation of several signal transduction pathways that elicit an anti-viral state and an anti-proliferative response. |
| T3 |
374-530 |
Sentence |
denotes |
Here, we quantitatively mapped the complete binding region of ifnar2 on interferon (IFN)alpha2 by 35 individual mutations to alanine and isosteric residues. |
| T4 |
531-766 |
Sentence |
denotes |
Of the six "hot-spot" residues identified (Leu-30, Arg-33, Arg-144, Ala-145, Met-148, and Arg-149), four are located on the E-helix, which is located at the center of the binding site flanked by residues on the A-helix and the AB-loop. |
| T5 |
767-944 |
Sentence |
denotes |
The contribution of residues of the D-helix, which have been previously implicated in binding, proved to be marginal for the interaction with the extracellular domain of ifnar2. |
| T6 |
945-1047 |
Sentence |
denotes |
Interestingly, the ifnar2 binding site overlaps the largest continuous hydrophobic patch on IFNalpha2. |
| T7 |
1048-1224 |
Sentence |
denotes |
Thus, hydrophobic interactions seem to play a significant role stabilizing this interaction, with the charged residues contributing toward the rapid association of the complex. |
| T8 |
1225-1508 |
Sentence |
denotes |
Relating the anti-viral and anti-proliferative activity of the various interferon mutants with their affinity toward ifnar2 results in linear function over the whole range of affinities investigated, suggesting that ifnar2 binding is the rate-determining step in cellular activation. |
| T9 |
1509-1666 |
Sentence |
denotes |
Dose-time analysis of the anti-viral response revealed that shortening the incubation time of low-level activation cannot be compensated by higher IFN doses. |
| T10 |
1667-1914 |
Sentence |
denotes |
Considering the strict dependence of the cellular response on affinity, these results suggest that for maintaining transcription of IFN-responsive genes over a longer time period, low but continuous signaling through the IFN receptor is essential. |
