Joe Loo
@joelooucla.bsky.social
270 followers
170 following
24 posts
UCLA Department of Chemistry and Biochemistry. Better living through mass spectrometry.
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Joe Loo
@joelooucla.bsky.social
· Jun 10
Joe Loo
@joelooucla.bsky.social
· Jun 9
Joe Loo
@joelooucla.bsky.social
· Jun 8
Joe Loo
@joelooucla.bsky.social
· May 22
Kermit Murray
@kkmurray.bsky.social
· May 22
Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase
A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organismal survival. While repair through methylation by PCMT1 has been previously shown to suppress L-isoaspartyl accumulation, we provide an additional mechanism for L-isoaspartyl maintenance through PCMTD1, a cullin-RING ligase (CRL). We combined cryo-EM, native mass spectrometry, and biochemical assays to provide insight on how the assembly and architecture of PCMTD1 in the context of a CRL complex fulfils this alternative mechanism. We show that the PCMTD1 CRL complex specifically binds L-isoaspartyl residues when bound to AdoMet. This work provides evidence for a growing class of E3 ubiquitin ligases that recognize spontaneous covalent modifications as potential substrates for ubiquitylation and subsequent proteasomal degradation.
dlvr.it
Reposted by Joe Loo
Joe Loo
@joelooucla.bsky.social
· Feb 4