2D IR indexing maps hIAPP helix-to-sheet kinetics
Paired 13C18O labels report dihedral angles: monomeric hIAPP is partly helical at L12A13, then oligomers lose helix and fibers form β-sheets.
Source
Site-specific detection of protein secondary structure using 2D IR dihedral indexing: a proposed assembly mechanism of oligomeric hIAPP
Study at a glance
- Design
- Other — 13C18O isotope-edited 2D IR of hIAPP secondary structure during aggregation
- N
- Biophysical spectroscopy of peptide aggregation — no cohort N
- Population
- Human islet amyloid polypeptide (hIAPP) monomers/oligomers
- Outcome
- Site-specific helix vs sheet coupling and aggregation kinetics
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
2D IR indexing maps hIAPP helix-to-sheet kinetics
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Helix nearest-neighbour coupling is +8.3 cm–1.
The coupling constant between residues adopting the dihedral angles of an α-helix is +8.3 cm –1 ( red dot, shows the structure).
Monomeric hIAPP in buffer is 20–38% α-helical at L12A13.
The data shown here establishes that the monomers of hIAPP in buffer are 20–38% α-helical at L12A13.
What they did
Authors 13C18O double-labelled neighbouring residues, calibrated couplings in SDS micelles, and recorded time-resolved 2D IR during aggregation versus singly labelled controls.
What they found
Helix coupling is +8.3 cm–1 vs +2.5 cm–1 in a β-sheet. Monomers are ~20–38% helical at L12A13; oligomers lack detectable helix; L12A13 shows three-state kinetics unlike two-state A13.
The limits
What it doesn't show
The leucine-rich-repeat oligomer model is postulated, not a high-resolution oligomer structure; only two labelled sites were tracked.
Key terms
- 2D IR spectroscopy
- Ultrafast infrared method that reports vibrational couplings as cross-peaks and frequency shifts.
- Dihedral indexing
- Using two neighbouring isotope labels so coupling signs/magnitudes report helix vs sheet dihedrals.
- hIAPP
- Human islet amyloid polypeptide (amylin) that aggregates in type 2 diabetes.
- Three-state kinetics
- Monomer → oligomer intermediate → fiber, resolved here at L12A13.
- 13C18O label
- Isotope pair that downshifts an amide I mode by ~65 cm–1.
Flashcards
0 of 11 answers reviewed
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
Quiz yourself
Dihedral indexing uses:
Common questions
How do helix and sheet couplings differ?
Helix ~+8.3 cm–1; nearest-neighbour β-sheet ~+2.5 cm–1 with opposite intensity pattern.
How helical is the monomer at L12A13?
About 20–38% (intensity ratios 27–38%).
Is the oligomer helical there?
No helix detected at L12A13 or L16V17 in the oligomer.
Why double labels?
Only pairs report dihedral coupling; single labels track fiber β-sheets.
More on Spectroscopy