Research: Proteins’ address book

15 January 2008

Researchers identify a structural code for moving SNARE proteins within a cell.

The organisation of a cell depends on its ability to distribute the proteins it makes to the places they are needed. For many proteins, this process involves being transported in vesicles, tiny sacs that are shuttled around the cell. Most proteins are sorted into the correct vesicles based on short sequence tags. Vesicle proteins called SNAREs help to ensure that the vesicles are shipped to the appropriate location. Now, a new mechanism for getting SNAREs into vesicles has been described by Wellcome Trust Senior Reseach Fellow David Owen, Principal Research Fellow Professor Margaret Robinson (both University of Cambridge) and colleagues.

The study revealed a web of interactions among three parts of the system. An outer scaffold, composed of the protein clathrin, helps to maintain the structure of the vesicle. The clathrin is linked to the vesicle surface by adaptor proteins, which recognise and bind to proteins that are destined for a specific location. One of these adaptor proteins (epsinR) binds very specifically to a particular SNARE (vti1b), but this binding does not involve a short sequence tag. Instead, a more complex recognition system, which depends on the overall fold or shape of the SNARE, allows the identification of key amino acid residues that mediate the binding between the adaptor and the SNARE. Mutating one of these residues in the SNARE caused it to become localised to an incorrect part of the cell.

Combined, this system links the recognition of a protein’s destination to the recognition and delivery of the correct target of the vesicle.

References

Miller SE et al. A SNARE–adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles. Nature 2007;450(7169):570-4.