2LP5: Native Structure of the Fyn SH3 A39V/N53P/V55L

Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a low-populated, on-pathway folding intermediate of the A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered in this intermediate, thereby exposing the aggregation-prone amino-terminal beta strand. Accordingly, mutants lacking the carboxyl terminus and thus mimicking the intermediate fail to safeguard the folding route and spontaneously form fibrillar aggregates. The structure provides a detailed characterization of the non-native interactions stabilizing an aggregation-prone intermediate under native conditions and insight into how such an intermediate can derail folding and initiate fibrillation.
PDB ID: 2LP5Download
MMDB ID: 99608
PDB Deposition Date: 2012/2/6
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2LP5: monomeric; determined by author
Molecular Components in 2LP5
Label Count Molecule
Protein (1 molecule)
Tyrosine-protein Kinase FYN(Gene symbol: FYN)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB