Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands.

Natural killer (NK) cells are effector cells of the innate immune system that distinguish between healthy and abnormal cells through activating and inhibitory receptor signaling. NKG2D, a homodimeric activating receptor expressed on NK cells, recognizes a diverse class of stress ligands expressed by cells experiencing infection, malignant transformation, chronic inflammation, and other cellular stresses. Despite the variety of NKG2D ligands, they all bind the receptor asymmetrically in a 1:1 ligand to homodimeric NKG2D stoichiometry.

Cryo-EM structure of ABCG5/G8 in complex with modulating antibodies.

The heterodimer of ATP-binding cassette transporter ABCG5 and ABCG8 mediates the excretion of sterols from liver and intestine, playing a critical role in cholesterol homeostasis. Here, we present the cryo-EM structure of ABCG5/G8 in complex with the Fab fragments from two monoclonal antibodies at 3.3Å resolution.

Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition.

The intestinal absorption of cholesterol is mediated by a multipass membrane protein, Niemann-Pick C1-Like 1 (NPC1L1), the molecular target of a cholesterol lowering therapy ezetimibe. While ezetimibe gained Food and Drug Administration approval in 2002, its mechanism of action has remained unclear. Here, we present two cryo-electron microscopy structures of NPC1L1, one in its apo form and the other complexed with ezetimibe.

Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab).

Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology. Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine. Aimovig is also the first FDA-approved mAb against a G-protein-coupled receptor (GPCR).

Molecular mechanism of an antagonistic antibody against glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in regulating glucose and lipid metabolism. GIP receptor (GIPR) antagonism is believed to offer therapeutic potential for various metabolic diseases. Pharmacological intervention of GIPR, however, has limited success due to lack of effective antagonistic reagents.

Crystal structure of the potassium-importing KdpFABC membrane complex.

Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four-subunit potassium pump that maintains intracellular homeostasis, cell shape and turgor under conditions in which potassium is limiting. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the superfamily of potassium transporters and another pump-like subunit (KdpB) belonging to the superfamily of P-type ATPases.

A novel six-rhodopsin system in a single archaeon.

Microbial rhodopsins, a diverse group of photoactive proteins found in Archaea, Bacteria, and Eukarya, function in photosensing and photoenergy harvesting and may have been present in the resource-limited early global environment. Four different physiological functions have been identified and characterized for nearly 5,000 retinal-binding photoreceptors, these being ion transporters that transport proton or chloride and sensory rhodopsins that mediate light-attractant and/or -repellent responses. The greatest number of rhodopsins previously observed in a single archaeon had been four.

Nephrogenic systemic fibrosis in advanced chronic kidney disease: a single hospital's experience in Taiwan.

Nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD) clinically resembles scleromyxedema which develops in the setting of advanced chronic kidney diseases. Limited data exist about its epidemiology in Asian countries. A total of 153 magnetic resonance imaging (MRI) examinations, including 81 contrast-enhancement, were identified in 127 patients with advanced chronic kidney disease at stage five undergoing MRI or angiography examination between January 2005 and July 2007, in our hospital.