PDBsum entry 2kqn

Immune system

PDB id: 2kqn

Contents

Protein chains

108 a.a. *

* Residue conservation analysis

PDB id:

2kqn

Name:

Immune system

Title:

Solution structure of the al-09 h87y immunoglobulin light chain variable domain

Structure:

Ig kappa chain v-i region au. Chain: a, b. Fragment: immunoglobulin kappa light chain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

B.F.Volkman,F.C.Peterson,M.Ramirez-Alvarado,E.M.Baden

Key ref:

F.C.Peterson et al. (2010). A single mutation promotes amyloidogenicity through a highly promiscuous dimer interface. Structure, 18, 563-570. PubMed id: 20462490

Date:

11-Nov-09 Release date: 16-Mar-10

Protein chains

No UniProt id for this chain

Struc: 108 a.a.

Structure 18:563-570 (2010)

PubMed id: 20462490

A single mutation promotes amyloidogenicity through a highly promiscuous dimer interface.

F.C.Peterson, E.M.Baden, B.A.Owen, B.F.Volkman, M.Ramirez-Alvarado.

ABSTRACT

Light chain amyloidosis is a devastating protein misfolding disease characterized by the accumulation of amyloid fibrils that causes tissue damage and organ failure. These fibrils are composed of monoclonal light chain protein secreted from an abnormal proliferation of bone marrow plasma cells. We previously reported that amyloidogenic light chain protein AL-09 adopts an altered dimer while its germline protein (kappaI O18/O8) forms a canonical dimer observed in other light chain crystal structures. In solution, conformational heterogeneity obscures all NMR signals at the AL-09 and kappaI O18/O8 dimer interfaces, so we solved the nuclear magnetic resonance structure of two related mutants. AL-09 H87Y adopts the normal dimer interface, but the kappaI Y87H solution structure presents an altered interface rotated 180 degrees relative to the canonical dimer interface and 90 degrees from the AL-09 arrangement. Our results suggest that promiscuity in the light chain dimer interface may promote new intermolecular contacts that may contribute to amyloid fibril structure.