M. R. Sawaya

A Suite of Designed Protein Cages Using Machine Learning Algorithms and Protein Fragment-Based Protocols

The paper designs new protein cages using machine learning and fragment-based methods, reporting their structures and insights into assembly success and failure.

DNAJB8 oligomerization is mediated by an aromatic-rich motif that is dispensable for substrate activity

This paper identifies an aromatic-rich motif in DNAJB8 that mediates oligomerization and shows that disrupting this motif affects oligomerization but not substrate activity.

Cryo-EM Structure of a Human LECT2 Amyloid Fibril Reveals a Network of Polar Ladders at its Core

This paper determines the cryo-EM structure of human LECT2 amyloid fibrils, revealing a tightly packed core stabilized by polar residues and hydrophobic contacts.

Structure of a reversible amyloid fibril formed by the CPEB3 prion-like domain reveals a core sequence involved in translational regulation

This study identifies an amyloidogenic segment in CPEB3's prion domain that is critical for its function in translational regulation and long-term memory.

Rigidified Scaffolds for 3-Angstrom Resolution Cryo-EM of Small Therapeutic Protein Targets

This paper demonstrates that rigidified scaffolds enable 3-angstrom resolution cryo-EM for small therapeutic proteins like KRAS, overcoming size limitations in structural characterization.

Cryo-EM structure of amyloid fibril formed by α-synuclein familial A53E mutation

The paper presents a cryo-EM structure of α-synuclein fibrils with the A53E mutation, showing structural differences that may affect aggregation kinetics and disease progression.

Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation

The paper presents a cryo-EM structure of RNA-bound tau fibrils, revealing a small C-terminal core that may nucleate fibril formation and is essential for fibril integrity.

Fragment-based ab initio phasing of peptidic nanocrystals by MicroED

This paper introduces a fragment-based method for de novo structure determination of peptidic nanocrystals using MicroED, enabling the solution of previously intractable structures.

Why amyloid fibrils have a limited width

The paper investigates why amyloid fibrils have a limited width, finding that helical symmetry causes hydrogen bonds to weaken at the fibril edges, preventing lateral growth beyond 10-20 nm.

Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2

The paper identifies amyloid-forming segments in SARS-CoV-2 Nucleoprotein and designs peptide inhibitors based on their atomic structures to target Covid-19.

CryoEM reveals how the small molecule EGCG binds to AD brain-derived tau fibrils and initiates fibril disaggregation

This study uses cryoEM to determine how EGCG binds to AD tau fibrils and initiates their disaggregation by wedging into a cleft and causing charge repulsions.

Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils

This study determines the cryo-EM structure of human IAPP fibrils and designs inhibitors to delay aggregation, offering insights into T2D pathology and therapeutic strategies.

The α-synuclein hereditary mutation E46K unlocks a more stable, pathogenic fibril structure

This study determines the cryoEM structure of α-synuclein fibrils with the E46K mutation, revealing a more stable and pathogenic fibril structure compared to wild-type.

Cryo-EM structures of alpha-synuclein fibrils with the H50Q hereditary mutation reveal new polymorphs

This study determines cryo-EM structures of alpha-synuclein fibrils with the H50Q mutation, revealing two new polymorphs and structural changes linked to disease mechanisms.

Cryo-EM Structures of Four Polymorphic TDP-43 Amyloid Cores

This study determines the cryo-EM structures of four polymorphic TDP-43 amyloid cores, revealing structural features that distinguish reversible from irreversible aggregation and how a mutation may enhance pathology.

Structure and mechanism of TagA, a novel membrane-associated glycosyltransferase that produces wall teichoic acids in pathogenic bacteria

This paper determines the structure of TagA, a glycosyltransferase involved in wall teichoic acid biosynthesis, and reveals its mechanism of catalysis and regulation by membrane interactions.

Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3 and ESX-5 type VII secretion systems

The paper reports crystal and SAXS structures of EspG chaperones from mycobacterial ESX systems, revealing structural variability and potential substrate binding modes.

Identification of two principal amyloid-driving segments in variable domains of Ig light chains in AL amyloidosis

The paper identifies two independent amyloid-driving segments in Ig light chain variable domains that drive fibril formation in AL amyloidosis and are potential therapeutic targets.