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Removal of a consensus proline is not sufficient to allow tetratricopeptide repeat oligomerization. Protein Sci 2017 Oct;26(10):1974-1983



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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 RB


Ronald Blake Hill PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Chromatography, Gel
Consensus Sequence
Membrane Proteins
Mitochondrial Proteins
Models, Molecular
Protein Domains
Protein Folding
Protein Multimerization
Recombinant Proteins
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc