Architectonic principles of polyproline II helix bundle protein domains

Rodríguez, Cristian Segura; Laurents, Douglas V.

doi:10.1016/j.abb.2024.109981

Archives of Biochemistry and Biophysics

2024

DOI: 10.1016/j.abb.2024.109981

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Architectonic principles of polyproline II helix bundle protein domains

Cristian Segura Rodríguez,

Douglas V. Laurents

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2024

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Cited by 3 publications

References 88 publications

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The C-terminal tails of GroEL and its mitochondrial and chloroplastic homologs adopt polyproline II helices

Rodríguez,

López-Sánchez,

Laurents

2024

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The chaperonin GroEL and its mitochondrial and chloroplastic homologs mHsp60 and Cpn60 are large barrel-like oligomeric proteins. Chaperonins facilitate folding by isolating nascent chains in their hollow interior and undergoing conformational transitions driven by ATP hydrolysis. Due to their vital importance, the structure of GroEL and its homologs have been extensively studied by X-ray crystallography and CryoEM, revealing one or two rings each of which contains seven subunits. Each subunit has three folded domains and a twenty-four residue C-terminal extension. Whereas this C-terminal tail has been reported to bind and stimulate the client protein folding, it appears to be invisible or poorly resolved, which suggests that it is disordered. The objective here is to characterize conformational preferences in the C-terminal tails of GroEL, mHsp60 and representative Cpn60s using circular dichroism and nuclear magnetic resonance spectroscopy methods. The tails of GroEL and mHsp60 consist of two segments. The first is rich in residues common in intrinsically disordered proteins, i.e. charged, proline, small like Ala, and polar. By contrast, the second segment is consists exclusively (GroEL) or almost entirely (mHsp60) of Gly and Met residues. The spectroscopic results evince that these C-terminal extensions, especially their second segments, are not wholly disordered but adopt high populations of PPII conformations. Regarding the plant cytoplastic chaperonins, whereas the C-terminal segments of Cpn60s are Gly-poor, they are rich in proline and also adopt PPII helix conformations. These results provide insight into the biological activities of the C-terminal tails.

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The C-terminal tails of GroEL and its mitochondrial and chloroplastic homologs adopt polyproline II helices

Rodríguez,

López-Sánchez,

Laurents

2024

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A Collagen Triple Helix without the Super Helical Twist

Kreutzberger,

Yu,

Hancu

et al. 2024

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Collagens are ubiquitous in biology functioning as the backbone of the extracellular matrix, forming the primary structural components of key immune system complexes, and fulfilling numerous other structural roles in a variety of systems. Despite this, there is limited understanding of how triple helices, the basic collagen structural units, pack into collagenous assemblies. Here we use a peptide self-assembly system to design collagenous assemblies based on the C1q collagen-like region. Using cryo-EM we solve a structure of one assembly to 3.5 Å resolution and build an atomic model. From this, we identify a triple helix conformation with no superhelical twist, starkly in contrast to the canonical right-handed triple helix. This non-twisting region allows for unique hydroxyproline stacking between adjacent triple helices and also results in the formation of an exposed cavity with rings of hydrophobic amino acids packed symmetrically. We find no precedent for such an arrangement of collagen triple helices and have designed mutant assemblies to probe key stabilizing amino acid interactions in the complex. The mutations behave as predicted by our atomic model. Our findings, combined with the extremely limited experimental structural data on triple helix packing in the literature, suggest that collagen and collagen-like assemblies may adopt a far more varied conformational landscape than previously appreciated. We hypothesize that this is particularly likely adjacent to the termini of these helices and at discontinuities to the required Xaa-Yaa-Gly repeating primary sequence; a discontinuity found in the majority of this class of proteins and in many collagen-associated diseases.

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Complex Hydrogen Bonding Leads to Cooperativity Between Antiparallel Polyproline Ii Helices

Laurents,

Sánchez,

Mompeán

2024

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Hydrogen bond cooperativity (HBC) is the phenomenon where the collective strengthening of hydrogen bonds in a network exceeds the sum of individual interactions due to mutual polarization and non-additive electrostatic effects. HBC has been well-studied in traditional protein secondary structures such as α-helices and β-sheets, where it critically stabilizes amyloid structures. In the last 20 years, several natural proteins have been characterized which contain several aligned and hydrogen-bonded polyproline II (PPII) helices. HBC has been recently reported for these PPII helices when they are arranged in parallel, but its existence in the more abundant antiparallel PPII helical assembly is still unknown.. By employing a battery of computational approaches validated through experimental observables, we report that both canonical CO···HN and non-canonical CO···HαCα hydrogen bonds exhibit mutual reinforcement, revealing a complex hydrogen bonding scheme that allows HBC in antiparallel PPII helices. These findings have fundamental relevance for our understanding of protein conformational stability and implications for PPII helices as a structural building block for protein design.

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Architectonic principles of polyproline II helix bundle protein domains

Cited by 3 publications

References 88 publications

The C-terminal tails of GroEL and its mitochondrial and chloroplastic homologs adopt polyproline II helices

The C-terminal tails of GroEL and its mitochondrial and chloroplastic homologs adopt polyproline II helices

A Collagen Triple Helix without the Super Helical Twist

Complex Hydrogen Bonding Leads to Cooperativity Between Antiparallel Polyproline Ii Helices

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