bioRxivJClub
Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1
bioRxiv · · Preprint · Open access
von Velsen, Juyoux + 6 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
Cryo-EM structures show that MEK1 activates ERK2 by releasing the MEK1 catalytic machinery upon MAPK substrate binding, with gain-of-function mutations enhancing this mechanism.
- Why it matters: Understanding how MAPK signalling maintains specificity and how ERK2 activation is coupled to upstream MEK1 interactions is still limited, despite pathway dysregulation driving many cancers.
- What they did: The study determined cryo-EM structures of MEK1 with ERK2 and used solution techniques plus molecular dynamics to probe substrate recognition and activation, including nucleotide exchange.
- The result: ERK2 release is not required for nucleotide exchange, supporting a processive mechanism, and the structural and mechanistic insights provide a starting point for drug development.
The findingWhy it mattersWhat they didThe result
- Open access