Removal of a consensus proline is not sufficient to allow tetratricopeptide repeat oligomerization. Protein Sci 2017 Oct;26(10):1974-1983
Date
07/15/2017Pubmed ID
28707340Pubmed Central ID
PMC5606541DOI
10.1002/pro.3234Scopus ID
2-s2.0-85026390100 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
Tetratricopeptide repeat (TPR) domains are ubiquitous protein interaction domains that adopt a modular antiparallel array of α-helices. The TPR fold typically adopts a monomeric state, and consensus TPRs sequences successfully fold into the expected monomeric topology. The versatility of the TPR fold also supports different quaternary structures, which may function as regulatory switches. One example is yeast mitochondrial fission 1 (Fis1) that appears to interconvert between monomer and dimer states in regulating division of peroxisomes and mitochondria. Whether human Fis1 can also interconvert like the yeast molecule is unknown. A TPR consensus proline residue present in human Fis1 is absent in the yeast molecule and, when added, prevents yeast Fis1 dimerization suggesting that the TPR consensus proline might have persisted to prevent TPR oligomerization. Here, we address this question with human Fis1 and the consensus TPR protein CTPR3. We demonstrate that human Fis1 does not form a noncovalent dimer via its TPR domain, despite conditions that favor dimerization of the yeast protein. We also show that the presence of the consensus proline is not sufficient to forbid TPR dimerization. Lastly, an analysis of all available TPR protein structures (22 nonredundant structures, totaling 64 TPRs-42 with the consensus proline and 22 without) revealed that the consensus proline is not necessary for turn formation, but does favor shorter turns. This work suggests the TPR consensus proline is not to prevent oligomerization, but to favor tight turns between repeats.
Author List
Bakkum AL, Hill RBMESH terms used to index this publication - Major topics in bold
Chromatography, GelConsensus Sequence
Humans
Membrane Proteins
Mitochondrial Proteins
Models, Molecular
Mutation
Proline
Protein Domains
Protein Folding
Protein Multimerization
Recombinant Proteins