**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Lindsey Lampe, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA

**Main Body of the Abstract**
The understanding of the mechanisms behind amyloid fibril formation in light-chain (AL) amyloidosis is currently limited.  However, it has been noted that AL amyloidosis patients often exhibit a high proportion of cysteinylated light chains. This work focuses on the C-terminus disulfide bond of human immunoglobulin control λ6a and amyloidogenic Wil full-length light chains, a subtype overrepresented in AL amyloidosis patients. These light chains can either be in a monomeric state due to cysteinylation of the C-terminus disulfide bond or form a homodimer with another free light chain at the C-terminus. For the purposes of this study, a cysteine to serine mutation was created at the C-terminus position of the λ6a and Wil light chains to study the monomeric form of these light chains. Methods including circular dichroism, thermal/urea unfolding followed via intrinsic fluorescence, Thioflavin T fibril formation assays, sedimentation assays, transmission electron microscopy, and mass spectrometry were used to study the secondary structures, stability, kinetics, and fibril formation of the λ6a and Wil light chains. Our findings indicate that the monomeric states (Cys to Ser mutant) of the λ6aand Wil light chains exhibit reduced stability, enhanced flexibility, and significantly increased tendency for fibril formation. Insights from this study hold great promise for enhancing our understanding of the mechanisms underlying fibril formation, patient prognosis, and the prospect of developing novel treatments for AL amyloidosis.



Role of the C-terminus disulfide bond in amyloid fibril formation of full-length human immunoglobulin λ6a and Wil light chains PA25 (#70)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.