2LP5

Native Structure of the Fyn SH3 A39V/N53P/V55L

Summary for 2LP5

• Entry DOI: 10.2210/pdb2lp5/pdb
• Related: 1SHF 2L2P 3CQT
• NMR Information: BMRB: 17149
• Descriptor: Tyrosine-protein kinase Fyn (1 entity in total)
• Functional Keywords: amyloid fibril, protein folding intermediate, transferase
• Biological source: Gallus gallus (bantam,chickens)
• Total number of polymer chains: 1
• Total formula weight: 7538.24

Authors

Neudecker, P.,Robustelli, P.,Cavalli, A.,Vendruscolo, M.,Kay, L.E. (deposition date: 2012-02-06, release date: 2012-05-16, Last modification date: 2024-05-15)

Primary citation

Neudecker, P.,Robustelli, P.,Cavalli, A.,Walsh, P.,Lundstrom, P.,Zarrine-Afsar, A.,Sharpe, S.,Vendruscolo, M.,Kay, L.E.
Structure of an intermediate state in protein folding and aggregation.
Science, 336:362-366, 2012

PubMed Abstract: 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 β 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.

PubMed: 22517863
DOI: 10.1126/science.1214203

Experimental method

SOLUTION NMR