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Structural Bioinformatics Studies of Integral Transmembrane Enzymes pMMO Complex, C560, CYB, and DHSD and their AlphaFold3-Predicted Water-Soluble QTY Variants

Jiayu Wang

Jiayu Wang

Phillips Exeter AcademyExeter, USA
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Wang, Jiayu
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Emily Pan

Emily Pan

Massachusetts Institute of TechnologyUSA
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Pan, Emily
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Shuguang Zhang

Shuguang Zhang

Media Lab, Massachusetts Institute of TechnologyUSA
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Zhang, Shuguang
  
28. Jan. 2025
Structural Bioinformatics Studies of Integral Transmembrane Enzymes pMMO Complex, C560, CYB, and DHSD and their AlphaFold3-Predicted Water-Soluble QTY Variants's Cover Image
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Artikel-Kategorie: Original study
Online veröffentlicht: 28. Jan. 2025
Seitenbereich: 79 - 89
DOI: https://doi.org/10.2478/biocosmos-2024-0006
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© 2024 Jiayu Wang et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1.

Experimental 1.5Å-resolution X-ray electron density maps of 20 amino acids arranged by size. This figure is provided by Dr. Mike Sawaya (UCLA), and used with permission in order to show the individual amino acid electron density maps at high resolution. The density maps demonstrate similar shapes of V and T; L, D, N, E and Q, and F and Y. Please see Dr. Mike Sawaya's original website: http://people.mbi.ucla.edu/sawaya/m230d/Modelbuilding/modelbuilding.html (courtesy of Dr. Michael R. Sawaya of University of California, Los Angeles, CA, USA).
Experimental 1.5Å-resolution X-ray electron density maps of 20 amino acids arranged by size. This figure is provided by Dr. Mike Sawaya (UCLA), and used with permission in order to show the individual amino acid electron density maps at high resolution. The density maps demonstrate similar shapes of V and T; L, D, N, E and Q, and F and Y. Please see Dr. Mike Sawaya's original website: http://people.mbi.ucla.edu/sawaya/m230d/Modelbuilding/modelbuilding.html (courtesy of Dr. Michael R. Sawaya of University of California, Los Angeles, CA, USA).

Figure 2.

Protein sequence alignments of six native protein sequences with their water-soluble QTY variants. The symbols | and *indicate whether amino acids are identical or different, respectively. The alpha helices (blue) are shown above the sequences. Alignments shown include a) pMOA vs pMOAQTY, b) pMOB vs pMOBQTY, c) pMOC vs pMOCQTY, d) CYB vs CYBQTY, e) C560 vs C560QTY, f) DHSD vs DHSDQTY.
Protein sequence alignments of six native protein sequences with their water-soluble QTY variants. The symbols | and *indicate whether amino acids are identical or different, respectively. The alpha helices (blue) are shown above the sequences. Alignments shown include a) pMOA vs pMOAQTY, b) pMOB vs pMOBQTY, c) pMOC vs pMOCQTY, d) CYB vs CYBQTY, e) C560 vs C560QTY, f) DHSD vs DHSDQTY.

Figure 3.

Superpositions of six Cryo-EM-determined structures of native oxidation enzymes and their AlphaFold3-predicted water-soluble QTY variants. The CryoEM-determined structures are obtained from the Protein Data Bank (PDB). The CryoEM structures (magenta) are superposed with their QTY variants (cyan) predicted by AlphaFold3. These superposed structures show that the native transporters and their QTY variants have very similar structures. For clarity of direct comparisons, unstructured loops in the CryoEM structures were removed in the QTY variants. a) pMOA vs pMOAQTY (0.302 Å), b) pMOB vs pMOBQTY (0.460 Å), c) pMOC vs pMOCQTY (0.590 Å), d) CYB vs CYBQTY (0.595 Å), e) C560 vs C560QTY (0.489 Å), and f) DHSD vs DHSDQTY (0.343 Å).
Superpositions of six Cryo-EM-determined structures of native oxidation enzymes and their AlphaFold3-predicted water-soluble QTY variants. The CryoEM-determined structures are obtained from the Protein Data Bank (PDB). The CryoEM structures (magenta) are superposed with their QTY variants (cyan) predicted by AlphaFold3. These superposed structures show that the native transporters and their QTY variants have very similar structures. For clarity of direct comparisons, unstructured loops in the CryoEM structures were removed in the QTY variants. a) pMOA vs pMOAQTY (0.302 Å), b) pMOB vs pMOBQTY (0.460 Å), c) pMOC vs pMOCQTY (0.590 Å), d) CYB vs CYBQTY (0.595 Å), e) C560 vs C560QTY (0.489 Å), and f) DHSD vs DHSDQTY (0.343 Å).

Figure 4.

Superpositions of AlphaFold3-predicted structures of native and their QTY variants. Color code: green = AlphaFold3-predicted native structures; cyan = AlphaFold3-predicted water-soluble QTY variants. a) C560AlphaFold3 vs C560QTY, b) CYBAlphaFold3 vs CYBQTY, c) DHSDAlphaFold3 vs DHSDQTY, d) pMOAAlphaFold3 vs pMOAQTY, e) pMOBAlphaFold3 vs pMOBQTY, and f) pMOCAlphaFold3 vs pMOCQTY.
Superpositions of AlphaFold3-predicted structures of native and their QTY variants. Color code: green = AlphaFold3-predicted native structures; cyan = AlphaFold3-predicted water-soluble QTY variants. a) C560AlphaFold3 vs C560QTY, b) CYBAlphaFold3 vs CYBQTY, c) DHSDAlphaFold3 vs DHSDQTY, d) pMOAAlphaFold3 vs pMOAQTY, e) pMOBAlphaFold3 vs pMOBQTY, and f) pMOCAlphaFold3 vs pMOCQTY.

Figure 5.

Superpositions of CryoEM structures with AlphaFold3-predicted native enzymes and their water-soluble QTY variants. Superposition of i) the experimentally determined CryoEM structures (magenta) with ii) AlphaFold3-predicted native transporters (green) and iii) AlphaFold3-predicted water-soluble QTY variant transporters (cyan). a) C560CryoEM vs C560AlphaFold3 vs C560QTY, b) CYBCryoEM vs CYBAlphaFold3 vs CYBQTY, c) DHSDCryoEM vs DHSDAlphaFold3 vs DHSDQTY, d) pMOACryoEM vs pMOAAlphaFold3 vs pMOAQTY, e) pMOBCryoEM vs pMOBAlphaFold3 vs pMOBQTY, and f) pMOCCryoEM vs pMOCAlphaFold3 vs pMOCQTY.
Superpositions of CryoEM structures with AlphaFold3-predicted native enzymes and their water-soluble QTY variants. Superposition of i) the experimentally determined CryoEM structures (magenta) with ii) AlphaFold3-predicted native transporters (green) and iii) AlphaFold3-predicted water-soluble QTY variant transporters (cyan). a) C560CryoEM vs C560AlphaFold3 vs C560QTY, b) CYBCryoEM vs CYBAlphaFold3 vs CYBQTY, c) DHSDCryoEM vs DHSDAlphaFold3 vs DHSDQTY, d) pMOACryoEM vs pMOAAlphaFold3 vs pMOAQTY, e) pMOBCryoEM vs pMOBAlphaFold3 vs pMOBQTY, and f) pMOCCryoEM vs pMOCAlphaFold3 vs pMOCQTY.

Figure 6.

Hydrophobic surface of six native proteins and their water-soluble QTY variants. The native oxidation enzymes have many hydrophobic residues L, I, V, and F in the transmembrane helices. After Q, T, and Y substitutions of L, I and V, and F respectively, the hydrophobic surface patches (yellow) in the transmembrane helices become more hydrophilic (cyan). a) pMOA vs pMOAQTY, b) pMOB vs pMOBQTY, c) pMOC vs pMOCQTY, d) CYB vs CYBQTY, e) C560 vs C560QTY, f) DHSD vs DHSDQTY.
Hydrophobic surface of six native proteins and their water-soluble QTY variants. The native oxidation enzymes have many hydrophobic residues L, I, V, and F in the transmembrane helices. After Q, T, and Y substitutions of L, I and V, and F respectively, the hydrophobic surface patches (yellow) in the transmembrane helices become more hydrophilic (cyan). a) pMOA vs pMOAQTY, b) pMOB vs pMOBQTY, c) pMOC vs pMOCQTY, d) CYB vs CYBQTY, e) C560 vs C560QTY, f) DHSD vs DHSDQTY.

RMSD and protein characteristic comparison between six selected native proteins and their QTY variants_

RMSD (Å) pI Mw (kDa) TM Variation (%) Overall Variation (%)
pMOACryoEM - 6.96 28.4252 - -
pMOAQTY 0.302 6.95 28.7047 44.44 22.67
pMOBCryoEM - 6.03 42.7860 - -
pMOBQTY 0.460 6.03 42.8397 33.33 3.66
pMOCCryoEM - 5.67 28.8514 - -
pMOCQTY 0.590 5.67 29.1388 41.98 22.00
CYBCryoEM - 7.82 42.7176 - -
CYBQTY 0.595 7.76 43.3619 51.48 22.89
C560CryoEM - 9.30 14.9700 - -
C560QTY 0.489 9.20 15.1600 86.61 19.12
DHSDCryoEM - 7.75 10.8887 - -
DHSDQTY 0.343 7.73 11.1701 35.38 22.33
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