Rational Design of Heterodimeric Protein using Domain Swapping for Myoglobin

Lin, Ying‐Wu; Nagao, Shigeaki; Zhang, Mohan; Shomura, Yasuhito; Higuchi, Yoshiki; Hirota, Shun

doi:10.1002/anie.201409267

Cited by 37 publications

(26 citation statements)

References 71 publications

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“…1,2,5,6,12,17,[34][35][36][37][38][39] As shown herein, we found that when an additional distal histidine was introduced in the heme pocket of F43Y Mb by L29H mutation, the double mutant L29H/F43Y Mb could form two distinct forms under different protein purification conditions, with and without the novel Tyr-heme cross-link between the Tyr43 and heme 4-vinyl groups. 1,2,5,6,12,17,[34][35][36][37][38][39] As shown herein, we found that when an additional distal histidine was introduced in the heme pocket of F43Y Mb by L29H mutation, the double mutant L29H/F43Y Mb could form two distinct forms under different protein purification conditions, with and without the novel Tyr-heme cross-link between the Tyr43 and heme 4-vinyl groups.…”

Section: Introductionsupporting

confidence: 72%

How a novel tyrosine–heme cross-link fine-tunes the structure and functions of heme proteins: a direct comparitive study of L29H/F43Y myoglobin

Yan

Yuan

et al. 2015

Dalton Trans.

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A heme-protein cross-link is a key post-translational modification (PTM) of heme proteins. Meanwhile, the structural and functional consequences of heme-protein cross-links are not fully understood, due to limited studies on a direct comparison of the same protein with and without the cross-link. A Tyr-heme cross-link with a C-O bond is a newly discovered PTM of heme proteins, and is spontaneously formed in F43Y myoglobin (Mb) between the Tyr hydroxyl group and the heme 4-vinyl group in vivo. In this study, we found that with an additional distal His29 introduced in the heme pocket, the double mutant L29H/F43Y Mb can form two distinct forms under different protein purification conditions, with and without a novel Tyr-heme cross-link. By solving the X-ray structures of both forms of L29H/F43Y Mb and performing spectroscopic studies, we made a direct structural and functional comparison in the same protein scaffold. It revealed that the Tyr-heme cross-link regulates the heme distal hydrogen-bonding network, and fine-tunes not only the spectroscopic and ligand binding properties, but also the protein reactivity. Moreover, the formation of the Tyr-heme cross-link in the double mutant L29H/F43Y Mb was investigated in vitro. This study addressed the key issue of how Tyr-heme cross-link fine-tunes the structure and functions of the heme protein, and provided a plausible mechanism for the formation of the newly discovered Tyr-heme cross-link.

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Section: Introductionsupporting

confidence: 72%

How a novel tyrosine–heme cross-link fine-tunes the structure and functions of heme proteins: a direct comparitive study of L29H/F43Y myoglobin

Yan

Yuan

et al. 2015

Dalton Trans.

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“…Domain swapping as envisioned for HemAC-Lm is a comparatively common characteristic among heme proteins, like cytochrome c [28][29][30][31], myoglobin [32,33], NO synthase [34], nitrite reductase [35], hemophore HasA [36] and methyl accepting chemotaxis protein [37]. However, the swapped Mb dimeric structure displays a similar oxygen-binding properties as that of its monomer [32].…”

Section: Discussionmentioning

confidence: 99%

Control of catalysis in globin coupled adenylate cyclase by a globin-B domain

Roy¹,

Santara²,

Adhikari³

et al. 2015

Archives of Biochemistry and Biophysics

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“…The resulting oligomer formed by this mechanism consists of subunits with the same structure as of the original monomer, except for the linking segments known as the hinge regions which connect the swapped domains (the secondary minor region) with the rest of the structure (the secondary major region). This oligomerization mechanism has been proposed for a wide range of proteins[15,18–24] where the size and nature of the swapped domains vary and may be as small as one secondary structural element or as large as a significant portion of the whole protein molecule. Likewise, the hinge region may be as small as consisting of three amino acids, but is it rarely larger than 15 amino-acids in length[21].…”

Section: Introductionmentioning

confidence: 99%

The enigma of the near-symmetry of proteins: Domain swapping

Bonjack-Shterengartz

Avnir

2017

PLoS ONE

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The majority of proteins form oligomers which have rotational symmetry. Literature has suggested many functional advantages that the symmetric packing offers. Yet, despite these advantages, the vast majority of protein oligomers are only nearly symmetric. A key question in the field of proteins structure is therefore, if symmetry is so advantageous, why do oligomers settle for aggregates that do not maximize that structural property? The answer to that question is apparently multi-parametric, and involves distortions at the interaction zones of the monomer units of the oligomer in order to minimize the free energy, the dynamics of the protein, the effects of surroundings parameters, and the mechanism of oligomerization. The study of this problem is in its infancy: Only the first parameter has been explored so far. Here we focus on the last parameter–the mechanism of formation. To test this effect we have selected to focus on the domain swapping mechanism of oligomerization, by which oligomers form in a mechanism that swaps identical portions of monomeric units, resulting in an interwoven oligomer. We are using continuous symmetry measures to analyze in detail the oligomer formed by this mechanism, and found, that without exception, in all analyzed cases, perfect symmetry is given away, and we are able to identify that the main burden of distortion lies in the hinge regions that connect the swapped portions. We show that the continuous symmetry analysis method clearly identifies the hinge region of swapped domain proteins–considered to be a non-trivial task. We corroborate our conclusion about the central role of the hinge region in affecting the symmetry of the oligomers, by a special probability analysis developed particularly for that purpose.

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Rational Design of Heterodimeric Protein using Domain Swapping for Myoglobin

Cited by 37 publications

References 71 publications

How a novel tyrosine–heme cross-link fine-tunes the structure and functions of heme proteins: a direct comparitive study of L29H/F43Y myoglobin

How a novel tyrosine–heme cross-link fine-tunes the structure and functions of heme proteins: a direct comparitive study of L29H/F43Y myoglobin

Control of catalysis in globin coupled adenylate cyclase by a globin-B domain

The enigma of the near-symmetry of proteins: Domain swapping

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