Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations.


Abstract

Electron paramagnetic resonance (EPR) spectroscopy of full-length vimentin and X-ray crystallography of vimentin peptides has provided concordant structural data for nearly the entire central rod domain of the protein. In this report, we use a combination of EPR spectroscopy and molecular modeling to determine the structure and dynamics of the missing region and unite the separate elements into a single structure. Validation of the linker 1-2 (L1-2) modeling approach is demonstrated by the close correlation between EPR and X-ray data in the previously solved regions. Importantly, molecular dynamic (MD) simulation of the constructed model agrees with spin label motion as determined by EPR. Furthermore, MD simulation shows L1-2 heterogeneity, with a concerted switching of states among the dimer chains. These data provide the first ever experimentally driven model of a complete intermediate filament rod domain, providing research tools for further modeling and assembly studies.

Submission Details

ID: Jd8BmmXZ

Submitter: David Gae

Submission Date: June 12, 2020, 11:14 a.m.

Version: 1

Publication Details
Hess JF, Budamagunta MS, Gae DD, McCarrick RM, Lorigan GA, Voss JC, FitzGerald PG,Structure (2019) Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations. PMID:31402219
Additional Information

Sequence of the structural domain covered in this paper. (Rod1B-L12-Rod2) GQGKSRLGDLYEEEMRELRRQVDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQELQAQIQEQHVQIDVDVSKPDLTAALRDVRQQYESVAAKNLQEAEEWYKSKFADLSEAANRNNDALRQAKQESTEYRRQVQSLTCEVDALK

Study Summary

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Human Vimentin P08670 VIME_HUMAN
93.8 Human Vimentin P48616 VIME_BOVIN
98.7 Human Vimentin P84198 VIME_CHLAE
98.7 Human Vimentin Q4R4X4 VIME_MACFA
98.7 Human Vimentin Q5R1W8 VIME_PANTR
97.2 Human Vimentin P02543 VIME_PIG
93.6 Human Vimentin P31000 VIME_RAT
93.6 Human Vimentin P20152 VIME_MOUSE
93.3 Human Vimentin P02544 VIME_MESAU
93.2 Human Vimentin P48670 VIME_CRIGR