Peptidomes and Structures Illustrate How SLA-I Micropolymorphism Influences the Preference of Binding Peptide Length
peer-reviewed · Frontiers in Immunology · 2022
| Date | 2022-02-28 |
| Type | peer-reviewed |
| Venue | Frontiers in Immunology |
| Publisher | Frontiers Media SA |
| Contribution | downstream-application |
| DOI | 10.3389/fimmu.2022.820881 |
| Citations (OpenAlex) | 9 |
Abstract
Polymorphisms can affect MHC-I binding peptide length preferences, but the mechanism remains unclear. Using a random peptide library combined with LC-MS/MS and de novo sequencing (RPLD-MS) technique, we found that two swine MHC-I molecules with high sequence homology, SLA-1*04:01 and SLA-1*13:01, had significant differences in length preference of the binding peptides. Compared with SLA-1*04:01, SLA-1*13:01 binds fewer short peptides with 8-10 amino acids, but more long peptides. A dodecapeptide peptide (RW12) can bind to both SLA-1*04:01 and SLA-1*13:01, but their crystal structures indicate that the binding modes are significantly different: the entirety of RW12 is embedded in the peptide binding groove of SLA-1*04:01, but it obviously protrudes from the peptide binding groove of SLA-1*13:01. The structural comparative analysis showed that only five differential amino acids of SLA-1*13:01 and SLA-1*04:01 were involved in the binding of RW12, and they determine the different ways of long peptides binding, which makes SLA-1*04:01 more restrictive on long peptides than SLA-1*13:01, and thus binds fewer long peptides. In addition, we found that the N terminus of RW12 extends from the groove of SLA-1*13:01, which is similar to the case previously found in SLA-1*04:01. However, this unusual peptide binding does not affect their preferences of binding peptide length. Our study will be helpful to understand the effect of polymorphisms on the length distribution of MHC-I binding peptides, and to screen SLA-I-restricted epitopes of different lengths and to design effective epitope vaccines.
Methods and tools
- Swine SLA-I peptide length preference (RPLD-MS): Random peptide library binding plus LC-MS/MS de novo sequencing (RPLD-MS) showed that swine SLA-1*13:01 binds more long peptides than SLA-1*04:01, explained by crystal structures.
Methods it uses
- PEAKS: Commercial DP-based de novo
Data deposited
- The length distribution of MHC-I binding peptides — as deposited · PXD020818
Cites (4)
- Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism (2021) both
- Structure and Peptidome of the Bat MHC Class I Molecule Reveal a Novel Mechanism Leading to High-Affinity Peptide Binding (2019) both
- Deep learning enables de novo peptide sequencing from data-independent-acquisition mass spectrometry (2018) both
- De novo peptide sequencing by deep learning (2017) both