Synthetic nanomaterials from standardized protein blocks

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Revision as of 01:15, 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)

In March, 2024, Huddy et al. in the team of David Baker (subsequently a Nobel Laureate) published a wide range of synthetic protein nanostructures self-assembled from standardized, engineered alpha-helical protein "building blocks"^[1] (). The extensively documented report, in Nature, has 32 authors^[1].

The breakthrough here is that instead of designing a single "one-off" desired nanostructure, the Baker group has first designed a series of regular building blocks that can be assembled into diverse nanostructures using straightforward geometric principles. These now enable "construction of protein nanomaterials according to ‘back of an envelope’ architectural blueprints"^[1]. There are many potential applications, such as drug delivery or catalysis, which remain to be explored.

1 Building Blocks
2 Assemblies
3 Related Work

Building Blocks

Click the green links below to change the molecular scene. Rotate to view the molecule from all sides (drag to rotate). Zoom with your mouse wheel, or Shift-Drag up/down.

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 ^[2]. 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 , 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.

Dozens of types of building blocks were designed, synthesized, purified, and their structures and assemblies were determined^[1]. ^[3].

Assemblies

Building blocks were designed with precise angles, and with specific points of attachment between blocks. Most self-assembled into the predicted assemblies^[4], including:

Flat Assemblies

(120_C3_A_design, branch 60°).
(90_C4_A_design, 90°).
(72_C5_A_design, 108°).
(R20A_design).
(strut_C6_21_cryo_fit).
(strut_C6_16_design).

Cage Assemblies

(cage_T3_5_+2_design).
(8TL7, 4.1 Å cryo-EM).
(cage_O4_32_design).
(8v2d, 6.8 Å cryo-EM, the initial scene).

Inter-Chain Adhesions

In , each chain (block) adheres to three other chains. . The surface of each chain is covered with a mixture of positive + and negative – charges. .

Related Work

Related work from the Baker group includes Bond-centric modular design of protein assemblies by Wang et al., 2024^[5].

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

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Eric Martz

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 In <scene name='10/1068508/Tetrahedron_8tl7_cao/1'>Tetrahedron A</scene>, each chain (block) adheres to three other chains. <scene name='10/1068508/Tetrahedron_8tl7_cao/2'>There are two "branch" adhesions (face to end) and one "handshake" adhesion (face-to-face)</scene>. The surface of each chain is covered with a mixture of <b><span class="text-blue">positive +</span></b> and <b><span class="text-red">negative –</span> charges. <scene name='10/1068508/8tl7_4_chains/1'>Here are four chains in greater detail</scene>.
+<jmol>
+ <jmolCheckbox>
+  <scriptWhenChecked>hide all</scriptWhenChecked>
+  <scriptWhenUnchecked>display all</scriptWhenUnchecked>
+  <text>tog vis</text>
+ </jmolCheckbox>
+</jmol>
 ==Related Work==

Synthetic nanomaterials from standardized protein blocks

From Proteopedia

Revision as of 01:15, 5 January 2025

Contents

Building Blocks

Assemblies

Flat Assemblies

Cage Assemblies

Inter-Chain Adhesions

Related Work

References

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