3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins
The aliphatic hydrophobic amino acid residues—alanine, isoleucine, leucine, proline and valine—are among the most common found in proteins. Their structural role in proteins is seemingly obvious: engage in hydrophobic interactions to stabilize secondary, and to a lesser extent, tertiary and quaterna...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1116868/full |
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| author | Mohammed H. AL Mughram Claudio Catalano Noah B. Herrington Martin K. Safo Glen E. Kellogg Glen E. Kellogg |
| author_facet | Mohammed H. AL Mughram Claudio Catalano Noah B. Herrington Martin K. Safo Glen E. Kellogg Glen E. Kellogg |
| author_sort | Mohammed H. AL Mughram |
| collection | DOAJ |
| description | The aliphatic hydrophobic amino acid residues—alanine, isoleucine, leucine, proline and valine—are among the most common found in proteins. Their structural role in proteins is seemingly obvious: engage in hydrophobic interactions to stabilize secondary, and to a lesser extent, tertiary and quaternary structure. However, favorable hydrophobic interactions involving the sidechains of these residue types are generally less significant than the unfavorable set arising from interactions with polar atoms. Importantly, the constellation of interactions between residue sidechains and their environments can be recorded as three-dimensional maps that, in turn, can be clustered. The clustered average map sets compose a library of interaction profiles encoding interaction strengths, interaction types and the optimal 3D position for the interacting partners. This library is backbone angle-dependent and suggests solvent and lipid accessibility for each unique interaction profile. In this work, in addition to analysis of soluble proteins, a large set of membrane proteins that contained optimized artificial lipids were evaluated by parsing the structures into three distinct components: soluble extramembrane domain, lipid facing transmembrane domain, core transmembrane domain. The aliphatic residues were extracted from each of these sets and passed through our calculation protocol. Notable observations include: the roles of aliphatic residues in soluble proteins and in the membrane protein’s soluble domains are nearly identical, although the latter are slightly more solvent accessible; by comparing maps calculated with sidechain-lipid interactions to maps ignoring those interactions, the potential extent of residue-lipid and residue-interactions can be assessed and likely exploited in structure prediction and modeling; amongst these residue types, the levels of lipid engagement show isoleucine as the most engaged, while the other residues are largely interacting with neighboring helical residues. |
| first_indexed | 2024-04-09T21:23:16Z |
| format | Article |
| id | doaj.art-f2ff01d0b7c34a5fa6fa2a27bb25f10f |
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| language | English |
| last_indexed | 2024-04-09T21:23:16Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-f2ff01d0b7c34a5fa6fa2a27bb25f10f2023-03-28T04:54:04ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-03-011010.3389/fmolb.2023.111686811168683D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteinsMohammed H. AL Mughram0Claudio Catalano1Noah B. Herrington2Martin K. Safo3Glen E. Kellogg4Glen E. Kellogg5Department of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesCenter for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA, United StatesThe aliphatic hydrophobic amino acid residues—alanine, isoleucine, leucine, proline and valine—are among the most common found in proteins. Their structural role in proteins is seemingly obvious: engage in hydrophobic interactions to stabilize secondary, and to a lesser extent, tertiary and quaternary structure. However, favorable hydrophobic interactions involving the sidechains of these residue types are generally less significant than the unfavorable set arising from interactions with polar atoms. Importantly, the constellation of interactions between residue sidechains and their environments can be recorded as three-dimensional maps that, in turn, can be clustered. The clustered average map sets compose a library of interaction profiles encoding interaction strengths, interaction types and the optimal 3D position for the interacting partners. This library is backbone angle-dependent and suggests solvent and lipid accessibility for each unique interaction profile. In this work, in addition to analysis of soluble proteins, a large set of membrane proteins that contained optimized artificial lipids were evaluated by parsing the structures into three distinct components: soluble extramembrane domain, lipid facing transmembrane domain, core transmembrane domain. The aliphatic residues were extracted from each of these sets and passed through our calculation protocol. Notable observations include: the roles of aliphatic residues in soluble proteins and in the membrane protein’s soluble domains are nearly identical, although the latter are slightly more solvent accessible; by comparing maps calculated with sidechain-lipid interactions to maps ignoring those interactions, the potential extent of residue-lipid and residue-interactions can be assessed and likely exploited in structure prediction and modeling; amongst these residue types, the levels of lipid engagement show isoleucine as the most engaged, while the other residues are largely interacting with neighboring helical residues.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1116868/fullhydrophobic residueshydropathic interactionssolvent-accessible surface area (SASA)membrane proteinslipid interactions |
| spellingShingle | Mohammed H. AL Mughram Claudio Catalano Noah B. Herrington Martin K. Safo Glen E. Kellogg Glen E. Kellogg 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins Frontiers in Molecular Biosciences hydrophobic residues hydropathic interactions solvent-accessible surface area (SASA) membrane proteins lipid interactions |
| title | 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins |
| title_full | 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins |
| title_fullStr | 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins |
| title_full_unstemmed | 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins |
| title_short | 3D interaction homology: The hydrophobic residues alanine, isoleucine, leucine, proline and valine play different structural roles in soluble and membrane proteins |
| title_sort | 3d interaction homology the hydrophobic residues alanine isoleucine leucine proline and valine play different structural roles in soluble and membrane proteins |
| topic | hydrophobic residues hydropathic interactions solvent-accessible surface area (SASA) membrane proteins lipid interactions |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1116868/full |
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