3.8 Protein and Nucleic Acid Folding: Domain Swapping in Proteins

Liu, Lin; Gronenborn, Angela M.

doi:10.1016/b978-0-12-374920-8.00309-x

Cited by 4 publications

(7 citation statements)

References 158 publications

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“…4,9-18 What seems to emerge as a common theme is that domain swapping is closely associated with the unfolding/folding process of proteins. Comparing the closed conformation of the monomeric polypeptide chain with the open conformation of the same chain in the domain-swapped structure does not immediately suggest a pathway by which all intra-molecular interactions can be replaced by inter-molecular ones.…”

Section: Introductionmentioning

confidence: 99%

“…Hydrophobic contacts, hydrogen-bonding, electrostatic interactions, and even disulfide bridges can be exchanged, and only the loop region in the monomer adopts a different conformation from the hinge in the domain-swapped dimer. 4,19 Therefore, starting with a folded monomer structure, the expectation would be that breaking and re-establishing interactions in conjunction with backbone conformational changes in the hinge-loop may require considerable energy. We call this energy the activation energy for 3D domain swapping starting from folded monomers.…”

Section: Introductionmentioning

confidence: 99%

“…We call this energy the activation energy for 3D domain swapping starting from folded monomers. 2,4 Folding from the unfolded polypeptide chain can result in either the closed monomer or the domain-swapped dimer, with partitioning between the two products determined by their free energy difference.…”

Section: Introductionmentioning

confidence: 99%

“…3 The analysis of their chain lengths, structural class or amino acid composition does not reveal any special properties, suggesting that almost any protein may be capable of undergoing domain swapping and that domain swapping is a specialized form of oligomer assembly. 4 Furthermore, domain swapping cannot be solely an in vitro artifact, given that some domain-swapped structures constitute biologically important species 5,6 or cause disease-related aggregation. 7,8 Therefore, understanding the mechanism of domain swapping is desirable.…”

Section: ■ Introductionmentioning

confidence: 99%

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Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein

et al. 2012

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Domain swapping creates protein oligomers by exchange of structural units between identical monomers. At present, no unifying molecular mechanism of domain swapping has emerged. Here we used the protein Cyanovirin-N and 19F-NMR to investigate the process of domain swapping. CV-N is an HIV inactivating protein that can exist as a monomer or a domain-swapped dimer. We measured thermodynamic and kinetic parameters of the conversion process and determined the size of the energy barrier between the two species. The barrier is very large and of similar magnitude to that for equilibrium unfolding of the protein. Therefore, for CV-N, overall unfolding of the polypeptide is required for domain swapping.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein

et al. 2012

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“…Currently, over 40 proteins are known that exhibit 3D domain swapping (30). The classical example is ribonuclease A (RNase A) (31).…”

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confidence: 99%

Different 3D domain-swapped oligomeric cyanovirin-N structures suggest trapped folding intermediates

Koharudin

Liu

Gronenborn

2013

Proc. Natl. Acad. Sci. U.S.A.

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Although it has long been established that the amino acid sequence encodes the fold of a protein, how individual proteins arrive at their final conformation is still difficult to predict, especially for oligomeric structures. Here, we present a comprehensive characterization of oligomeric species of cyanovirin-N that all are formed by a polypeptide chain with the identical amino acid sequence. Structures of the oligomers were determined by X-ray crystallography, and each one exhibits 3D domain swapping. One unique 3D domainswapped structure is observed for the trimer, while for both dimer and tetramer, two different 3D domain-swapped structures were obtained. In addition to the previously identified hinge-loop region of the 3D domain-swapped dimer, which resides between strands β5 and β6 in the middle of the polypeptide sequence, another hinge-loop region is observed between strands β7 and β8 in the structures. Plasticity in these two regions allows for variability in dihedral angles and concomitant differences in chain conformation that results in the differently 3D domain-swapped multimers. Based on all of the different structures, we propose possible folding pathways for this protein. Altogether, our results illuminate the amazing ability of cyanovirin-N to proceed down different folding paths and provide general insights into oligomer formation via 3D domain swapping.CV-N | NMR spectroscopy | protein folding | X-ray structures

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Domain swapping of the C‐terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis

Kim

Chang

et al. 2023

Protein Science

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Polyketide metabolism-associated proteins in Mycobacterium tuberculosis play an essential role in the survival of the bacterium, which makes them potential drug targets for the treatment of tuberculosis (TB). The novel ribonuclease protein Rv1546 is predicted to be a member of the steroidogenic acute regulatory protein-related lipid-transfer (START) domain superfamily, which comprises bacterial polyketide aromatase/cyclases (ARO/CYCs). Here, we determined the crystal structure of Rv1546 in a V-shaped dimer. The Rv1546 monomer consists of four α-helices and seven antiparallel β-strands. Interestingly, in the dimeric state, Rv1546 forms a helix-grip fold, which is present in START domain proteins, via three-dimensional domain swapping. Structural analysis revealed that the conformational change of the C-terminal α-helix of Rv1546 might contribute to the unique dimer structure. Site-directed mutagenesis followed by in vitro ribonuclease activity assays was performed to identify catalytic sites of the protein. This experiment suggested that surface residues R63, K84, K88, and R113 are important in the ribonuclease function of Rv1546. In summary, this study presents the structural and functional characterization of Rv1546 and supplies new perspectives for exploiting Rv1546 as a novel drug target for TB treatment.

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3.8 Protein and Nucleic Acid Folding: Domain Swapping in Proteins

Cited by 4 publications

References 158 publications

Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein

Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein

Different 3D domain-swapped oligomeric cyanovirin-N structures suggest trapped folding intermediates

Domain swapping of the C‐terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis

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3.8 Protein and Nucleic Acid Folding: Domain Swapping in Proteins

Cited by 4 publications

References 158 publications

Domain Swapping Proceeds via Complete Unfolding: A 19F- and 1H-NMR Study of the Cyanovirin-N Protein

Domain Swapping Proceeds via Complete Unfolding: A 19F- and 1H-NMR Study of the Cyanovirin-N Protein

Different 3D domain-swapped oligomeric cyanovirin-N structures suggest trapped folding intermediates

Domain swapping of the C‐terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis

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Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein

Domain Swapping Proceeds via Complete Unfolding: A ¹⁹F- and ¹H-NMR Study of the Cyanovirin-N Protein