Synthetic nanomaterials from standardized protein blocks
From Proteopedia
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In this project, the simplest building blocks consist of anti-parallel alpha helices engineered to be straight and flat, that is ''twistless helix repeat'' (THR) protein blocks. A simple example, THR1, is [[8g9j]], consisting of <scene name='10/1068508/8g9j_flat_square/3'>eight anti-parallel alpha helices with seven turns per helix</scene><ref>An amino-terminal histidine tag was not resolved in the electron density map of [[8g9j]], and thus is missing in the structure depicted.</ref>. Each helix is amphipathic, that is, hydrophobic on the side contacting other helixes, and hydrophilic on the side facing outwards (not shown). The 2.5 Å [[resolution]] of [[8g9j]] enabled the modeling of all helix side chains. Non-covalent interactions between helices are nearly all apolar, with a few hydrogen bonds, and two salt bridges (not shown). The <scene name='10/1068508/8g9j_flat_square/4'>block surface is designed to have many charges</scene>, making a highly water soluble building block. The edges of the block are "capped" with charges that prevent these blocks from binding to each other, thus enabling crystallization of this block rather than having it precipitate. | In this project, the simplest building blocks consist of anti-parallel alpha helices engineered to be straight and flat, that is ''twistless helix repeat'' (THR) protein blocks. A simple example, THR1, is [[8g9j]], consisting of <scene name='10/1068508/8g9j_flat_square/3'>eight anti-parallel alpha helices with seven turns per helix</scene><ref>An amino-terminal histidine tag was not resolved in the electron density map of [[8g9j]], and thus is missing in the structure depicted.</ref>. Each helix is amphipathic, that is, hydrophobic on the side contacting other helixes, and hydrophilic on the side facing outwards (not shown). The 2.5 Å [[resolution]] of [[8g9j]] enabled the modeling of all helix side chains. Non-covalent interactions between helices are nearly all apolar, with a few hydrogen bonds, and two salt bridges (not shown). The <scene name='10/1068508/8g9j_flat_square/4'>block surface is designed to have many charges</scene>, making a highly water soluble building block. The edges of the block are "capped" with charges that prevent these blocks from binding to each other, thus enabling crystallization of this block rather than having it precipitate. | ||
| - | === | + | ===Five types of building blocks=== |
Dozens of types of building blocks were designed, synthesized, purified, and their structures and assemblies were determined<ref name="huddy2024" />. <scene name='10/1068508/5_building_block_modules/1'>Here are shown five examples having specified angles within or between pairs of protein chains</scene><ref>The five modules shown are from the following assemblies that can be downloaded as PDB files from supplementary materials of Huddy ''et al,'', 2024: 90° from strut_C6_16. Branch from TT_rail+_tie+. Curve from R20A. Handshake 90° from cage_O4_32. Handshake obtuse angle from cage_I3_8.</ref>. | Dozens of types of building blocks were designed, synthesized, purified, and their structures and assemblies were determined<ref name="huddy2024" />. <scene name='10/1068508/5_building_block_modules/1'>Here are shown five examples having specified angles within or between pairs of protein chains</scene><ref>The five modules shown are from the following assemblies that can be downloaded as PDB files from supplementary materials of Huddy ''et al,'', 2024: 90° from strut_C6_16. Branch from TT_rail+_tie+. Curve from R20A. Handshake 90° from cage_O4_32. Handshake obtuse angle from cage_I3_8.</ref>. | ||
Revision as of 02:17, 5 January 2025
This page is under construction. This notice will be removed when it is ready. Eric Martz 21:20, 23 December 2024 (UTC) |
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References
- ↑ 1.0 1.1 1.2 1.3 Huddy TF, Hsia Y, Kibler RD, Xu J, Bethel N, Nagarajan D, Redler R, Leung PJY, Weidle C, Courbet A, Yang EC, Bera AK, Coudray N, Calise SJ, Davila-Hernandez FA, Han HL, Carr KD, Li Z, McHugh R, Reggiano G, Kang A, Sankaran B, Dickinson MS, Coventry B, Brunette TJ, Liu Y, Dauparas J, Borst AJ, Ekiert D, Kollman JM, Bhabha G, Baker D. Blueprinting extendable nanomaterials with standardized protein blocks. Nature. 2024 Mar;627(8005):898-904. PMID:38480887 doi:10.1038/s41586-024-07188-4
- ↑ An amino-terminal histidine tag was not resolved in the electron density map of 8g9j, and thus is missing in the structure depicted.
- ↑ The five modules shown are from the following assemblies that can be downloaded as PDB files from supplementary materials of Huddy et al,, 2024: 90° from strut_C6_16. Branch from TT_rail+_tie+. Curve from R20A. Handshake 90° from cage_O4_32. Handshake obtuse angle from cage_I3_8.
- ↑ The assemblies shown can be downloaded as PDB files from supplementary materials of Huddy et al,, 2024.
- ↑ Wang S, Favor A, Kibler R, Lubner J, Borst AJ, Coudray N, Redler RL, Chiang HT, Sheffler W, Hsia Y, Li Z, Ekiert DC, Bhabha G, Pozzo LD, Baker D. Bond-centric modular design of protein assemblies. bioRxiv [Preprint]. 2024 Oct 12:2024.10.11.617872. PMID:39416012 doi:10.1101/2024.10.11.617872
