Cryo-EM structure of the activated RET signaling complex reveals the importance of its cysteine-rich domain

Tyck till om SwePub Sök här!

Bigalke, Janna M. (författare)

Aibara, Shintaro (författare): Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)

Roth, Robert (författare)

Dahl, Göran (författare)

Gordon, Euan (författare)

Dorbéus, Sarah (författare)

Amunts, Alexey (författare): Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Karolinska Institutet, Sweden

Sandmark, Jenny (författare)

(creator_code:org_t)

American Association for the Advancement of Science (AAAS), 2019
2019
Engelska.
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:7

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://doi.org/10.1...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; visa färre...

Abstract Ämnesord

Stäng

Signaling through the receptor tyrosine kinase RET is essential during normal development. Both gain- and loss-of-function mutations are involved in a variety of diseases, yet the molecular details of receptor activation have remained elusive. We have reconstituted the complete extracellular region of the RET signaling complex together with Neurturin (NRTN) and GFR alpha 2 and determined its structure at 5.7-angstrom resolution by cryo-EM. The proteins form an assembly through RET-GFR alpha 2 and RET-NRTN interfaces. Two key interaction points required for RET extracellular domain binding were observed: (i) the calcium-binding site in RET that contacts GFR alpha 2 domain 3 and (ii) the RET cysteine-rich domain interaction with NRTN. The structure highlights the importance of the RET cysteine-rich domain and allows proposition of a model to explain how complex formation leads to RET receptor dimerization and its activation. This provides a framework for targeting RET activity and for further exploration of mechanisms underlying neurological diseases.

Av författaren/redakt...: Bigalke, Janna M ...; Aibara, Shintaro; Roth, Robert; Dahl, Göran; Gordon, Euan; Dorbéus, Sarah; visa fler...; Amunts, Alexey; Sandmark, Jenny; visa färre...

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.