There is a constancy in protein structure throughout biology and also small MW molecules influence their biological activity. A major protein , small molecular weight interaction occurs at receptors.
I have long felt that the hormones that are active in the other Kingdoms e.g. plants may well have import in man. Obvious, so obvious examples are the vitamins and trace elements.
A very important plant hormone is auxin. This is produced in regions of actively dividing and enlarging cells that regulate plant growth. The action is to modulate gene expression and hence cell division, elongation and differentiation. The auxins include 3-acetic acid and indole-3-acetonitrile.
Their importance is shown by their availability in every Plant Nursery Shop or Garden Centre for rooting.
How the auxin works is still being studied.
Auxin is recognised by a small family of F-box proteins including transport inhibitor response 1 (TIR1. Auxin regulates gene expression by promoting SCF ubiquitin-ligase-catalysed degradation of the Aux/I AA transcription repressors, but how the TIR1 F-box protein senses and becomes activated by auxin remains unclear. In a recent paper in Nature crystal structures of the Arabidopsis TIR1-ASK1 complex show that the leucine-rich repeat domain of TIR1 contains an unexpected inositol hexakisphosphate co-factor and recognizes auxin and the Aux/I AA polypeptide substrate through a single surface pocket. Anchored to the base of the TIR1 pocket, auxin binds to a partially favourable site, which can also accommodate various auxin analogues. Docked on top of auxin, the Aux/IAA substrate peptide occupies the rest of the TIR1 pocket and completely encloses the hormone-binding site. By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIRI-substrate interactions by acting as a ‘molecular glue.
In plants, multiple phytohormone signalling pathways are now known to be regulated by ubiquitin ligases. In particular, jasmonic acid signalling requires COI1, an F-box protein with high sequence similarity to TIRT. It is feasible that COIl adopts a TIRl-like structure and possibly functions as a jasmonic acid receptor. Most of the auxin-contacting residues in T1RI are indeed not conserved in COI1. Although TIRI orthologues, so far are only found in plants, a small ligand-sensing site regulating substrate recruitment could conceivably be evolved in a different structural context in other human ubiquitin ligases.
An increasing number of human disorders has now been associated with defective ubiquitin-ligase-substrate interactions owing to mutations of the ligases themselves, ubiquitination substrates or upstream signalling proteins responsible for substrate priming. The regulator.’ mechanism of TIKI by auxin suggests that it is possible for small molecules to promote protein-protein interactions in ubiquitin ligases. and potentially other protein interaction systems that arc impaired by genetic alterations.
When we eat plants and presumably ingest auxins do these compounds play a necessary par in our metabolism. A wonderful research project
Tan et al 2007 Nature April 5th vol 446, pp 640-644
Guilfoyle 2007 Nature April 5th vol 446 pp 621-2
- Martin Eastwood