lmmol Reviews
- AAA ATPase systems: disaggregation, remodeling, and proteostasis leverage
AAA ATPases are now best interpreted as molecular extractors: they couple repeated ATP hydrolysis cycles to forceful protein remodeling in many cellular compartments . In modern literature, the…
- Fibronectin type-III domains: extracellular recognition and signaling interfaces
Fibronectin type-III (FN3) repeats are not passive adhesion fragments; in modern mammalian and developmental biology they are treated as context-switch modules that tune receptor geometry, matrix…
- PP-binding proteins: modularity, scaffolding, and the modern polyketide frontier
PP-binding proteins anchor non-ribosomal and polyketide chemistry by carrying reactive carboxylate intermediates through repeated, domain-encoded steps. Across bacterial and fungal systems, the same…
- bHLH transcription factors: control logic, developmental memory, and metabolic timing
bHLH proteins sit at the boundary between sequence grammar and cellular state, using dimerization-dependent DNA recognition to coordinate developmental, metabolic, and circadian programs . The modern…
- Short-chain dehydrogenase/reductases: endocrine and redox control in metabolism
The short-chain dehydrogenase/reductase (SDR) superfamily is a compact catalytic scaffold with broad physiological reach, especially in hormone conversion, lipid processing, and stress-linked redox…
- Alcohol dehydrogenase N-domain biology: redox versatility across systems
PF08240 covers the N-terminal catalytic platform of zinc-dependent alcohol dehydrogenases, a family conserved from bacteria to humans . Across organisms, the same fold supports metabolic…
- Ketoacyl-synthase systems: modular fatty-acid builders as therapeutic and control nodes
Ketoacyl-synthase (KS) domains continue to define how organisms expand fatty-acid and polyketide architecture. The family has a dual identity: a homeostatic metabolic core in primary biosynthesis and…
- Ketoacyl-synthase C-domain and the logic of chain extension
Ketoacyl-synthase C-terminal architecture (PF02801) is where polyketide synthase logic becomes experimentally concrete: modules are not abstract annotations, they are executable catalytic programs.…
- Acyltransferase-1 systems: chain-building handoff and pathway retuning
Acyltransferase-1 proteins mediate the handoff between acyl donors and downstream chain-building modules, making them central in both fatty-acid and polyketide assembly logic . The family is less a…
- RNA-dependent RNA polymerases: replication engines, adaptation, and intervention points
RNA-dependent RNA polymerase (RdRp) domains define the operational core of many positive-strand RNA virus programs, and the literature now frames this enzyme family as a coordination layer between…
- Innate immune sentinels: LRR_6 receptor scaffolds in pattern recognition
Leucine-rich-repeat 6-domain proteins are recurring scaffolds that couple danger detection to inflammation with a shared architecture: modular sensing, adaptor recruitment, and controlled activation…
- Fungal Zn2Cys6 transcription factors: network logic in adaptation and resistance
Zn2Cys6 (Zn_clus) regulators are modular transcriptional program builders: the DNA-binding grammar is broadly conserved, while organismal outputs vary with developmental state and ecological pressure…
- TRIM/B-box and KRAB-associated proteins: chromatin, innate immunity, and transcriptional control
The zf-B_box-associated protein family has moved from a structural footnote to a central layer of immune, developmental, and chromatin regulation biology . Modern studies now treat B-box TRIM…
- Reducing modules in type I polyketide systems: chain-programming and pathway control
The PKS_DH_N module anchors β-keto reduction in type I polyketide synthase systems, where domain geometry and timing can determine chain topology as much as raw catalytic potential . The field has…
- Polyketide synthase dehydrogenase (PS-DH): branch-point chemistry and pathway choice
PF14765 (PS-DH) sits at a recurring branch point where polyketide pathways decide reduction state, ring topology, and final bioactivity. In pathway terms, these dehydrogenase steps are often the…
- Iterative polyketide reductive modules: module-level gatekeeping in secondary metabolism
KR-containing segments in type I assembly lines are best read as chain-logic modules inside a larger scaffolded pathway, not as isolated reductase chemistry . Pathway context determines output as…
- Condensation domains: programming logic in nonribosomal peptide synthesis
Condensation (C) domains in nonribosomal peptide synthetases coordinate both chemistry and topology: they define how activated intermediates are passed forward and thus govern final peptide…
- Ketosynthase-associated C-terminal domains: extension control in modular polyketide synthases
The KAsynt_C_assoc neighborhood is best understood as pathway-coupling machinery: C-terminal-associated domains stabilize productive chain transfer and shape where and how modules hand off chemistry.
- LRR receptors and repeats: surface sensing to signaling breadth
Leucine-rich repeat (LRR) architectures persist as one of biology’s most durable ways to sense shape, chemistry, and pattern. Across immunity, neurobiology, and membrane signaling, LRR modules keep…
- AMP-binding enzymes: adenylate activation as a leverage point in metabolism and stress
AMP-binding domains are among the most recurrent catalytic solutions for activating carboxylates into high-energy intermediates. The modern review frame treats this chemistry as a gateway: one…
- Dynamic SET-domain methylation in development, differentiation, and disease
The SET domain continues to sit at the core of epigenetic regulation because it converts substrate choice into persistent chromatin programs. The family has long been known to set repressive and…
- SH2 domains: how docking modules reshape signaling and immune control in the 2020s
- Protein Tyrosine Kinases (PF07714): Receptors, Fusions, and the Expanding Therapeutic Frontier
The PK_Tyr_Ser-Thr domain (Pfam PF07714) defines the catalytic core shared by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases, a family of 1168 proteins spanning 5148 papers in…
- Voltage-Gated Ion Channels: The Ion_trans Domain (PF00520) in the Cryo-EM Era
The Ion_trans domain (Pfam PF00520) is the shared structural core of voltage-gated sodium (Na_v), potassium (K_v), and calcium (Ca_v) channels — the molecular machines that generate and propagate the…
- DEAD-box RNA helicases: ATP-dependent RNA remodeling from translation to condensates
DEAD-box RNA helicases (Pfam PF00270) are a large family of ATP-dependent enzymes that remodel RNA and RNA-protein complexes at nearly every step of gene expression, including translation initiation,…
- Wnt/β-catenin signaling as a system: from lipidated ligands to TCF-driven transcription
The Wnt/β-catenin ("canonical") pathway is a cross-family signaling system that converts an extracellular cue into a nuclear transcriptional decision. Secreted Wnt ligands engage Frizzled receptors…
- Major Facilitator Superfamily transporters: recent advances in structure, mechanism, and therapeutic targeting
The Major Facilitator Superfamily (MFS, Pfam MFS_1, PF07690) is the largest group of secondary membrane transporters in the cell . Foundational structural work on the bacterial glycerol-3-phosphate…
- The inflammasome: assembly, caspase-1 activation, and gasdermin-driven pyroptosis
The inflammasome is a cytosolic supramolecular platform of innate immunity that converts the detection of infection and cellular "danger" into a rapid, inflammatory cell-death response. The concept…
- TGF-β / SMAD Signaling: A Cross-Family Pathway from Ligand to Transcription
The transforming growth factor beta (TGF-β) family is a large group of secreted growth and differentiation factors that control the development and homeostasis of most tissues in metazoan organisms .…
- The 26S Proteasome: A Two-Particle Machine for Ubiquitin-Dependent Degradation
The 26S proteasome is the central protease of the ubiquitin-proteasome system, executing the regulated, ATP-dependent degradation of cytoplasmic and nuclear proteins. It is built from two…
- Deubiquitinating enzymes: reversing ubiquitination as a therapeutic frontier
Ubiquitination is a reversible post-translational modification central to many biological processes, including the cell cycle, DNA repair, apoptosis, and immune signaling. Deubiquitinating enzymes…
- Heterotrimeric G-protein signaling: the Gαβγ heterotrimer and its GTPase cycle
Heterotrimeric G proteins are the central relay that converts ligand binding at G-protein-coupled receptors (GPCRs) into intracellular responses. The receptor, a seven-transmembrane (7TM) protein,…
- The Autophagy Machinery: A Cross-Family View of the ATG System
Macroautophagy is a conserved catabolic process in which cytoplasmic components are enclosed by double-membrane autophagosomes and delivered to the lysosome or vacuole for degradation, a route…
- Cohesin and Sister-Chromatid Cohesion: A Ring-Shaped Machine for Genome Cohesion and 3D Organization
Cohesin is a multisubunit complex that holds replicated sister chromatids together from S phase until anaphase, opposing the splitting force exerted by spindle microtubules so that chromosomes…
- Notch signaling as a system: ligand engagement, regulated proteolysis, and CSL-mediated transcription
Notch signaling is a conserved, juxtacrine pathway that governs metazoan development and adult tissue renewal, and its misregulation underlies developmental syndromes, adult-onset arteriopathy, and…
- SNARE-Mediated Membrane Fusion and Neurotransmitter Release: Assembly, Triggering, and Disease
Fast chemical neurotransmission depends on the regulated fusion of synaptic vesicles with the presynaptic plasma membrane, a reaction catalyzed by a conserved set of SNARE (soluble…
- N6-methyladenosine (m6A) mRNA Methylation: Writers, Readers, and Erasers of the Epitranscriptome
N6-methyladenosine (m6A) is the most prevalent internal modification in the messenger RNA of all higher eukaryotes . Transcriptome-wide mapping by m6A-seq first revealed the human and mouse m6A…
- Eukaryotic Protein Kinases: A Survey of the Pkinase Family (PF00069)
Eukaryotic protein kinases constitute one of the largest and most functionally consequential protein families, transducing signals by transferring phosphate onto serine, threonine, and tyrosine…
- Rhodopsin-like GPCRs (Pfam 7tm_1, class A): from cloning-era pharmacology to G-protein-complex structures
The rhodopsin-like family (Pfam 7tm_1, class A G-protein-coupled receptors) is the largest and most pharmacologically important group of cell-surface signaling proteins, sharing a bundle of seven…
- Helicase_C (PF00271): Superfamily 2 Helicases from RNA Sensing to Chromatin Remodeling and Genome Stability
The Helicase_C domain (PF00271) marks the C-terminal RecA-like lobe of superfamily 2 (SF2) helicases, a vast and functionally diverse clade united by ATP-dependent translocation along nucleic acids.…
- ATP-Binding Cassette (ABC) Transporters: From Disease Genes to Cryo-EM Mechanism
ATP-binding cassette (ABC) transporters are a ubiquitous superfamily of membrane proteins that couple ATP hydrolysis to the translocation of chemically diverse substrates across cell membranes, with…
- Cytochrome P450 Monooxygenases: Heme-Thiolate Catalysts of Drug Metabolism and Steroidogenesis
Cytochrome P450 (CYP) enzymes form a vast superfamily of heme-thiolate monooxygenases that add molecular oxygen to non-activated hydrocarbons at physiological temperature, a reaction that otherwise…
- WD40-Repeat (β-Propeller) Proteins: Interaction Hubs at the Heart of Cellular Assembly
The WD40 repeat (PF00400) is one of the most abundant protein-interaction modules in eukaryotes. Each repeat, roughly 40 residues ending in a Trp-Asp dipeptide, contributes a four-stranded…
- C2H2-type zinc finger transcription factors: from the recognition code to genome architecture
The Cys2-His2 (C2H2) zinc finger (Pfam PF00096, topic zf-C2H2) is among the most abundant DNA-binding modules in eukaryotic transcription factors. The motif was first defined biochemically in Xenopus…
- RNA Recognition Motif (RRM) Proteins: From Splicing Machines to Phase-Separating Drivers of ALS-FTD
The RNA recognition motif (RRM, Pfam PF00076) is among the most abundant RNA-binding folds in eukaryotes, deployed across pre-mRNA splicing, polyadenylation, mRNA export, stability, and translation.…
- Homeodomain transcription factors: developmental patterning from HOX clusters to single-cell identity codes
The homeodomain (Pfam PF00046) is a ~60-residue helix-turn-helix DNA-binding module that defines one of the largest and most ancient families of developmental transcription factors. Originally…
- SH3 domains: proline-rich recognition, Src-family kinase autoinhibition, and adaptor signaling
The Src homology 3 (SH3) domain is one of the most widespread modular protein-interaction units in metazoan signaling. SH3 domains classically engage proline-rich peptide ligands and, in the context…
- Ankyrin-repeat proteins: tandem scaffolds at the heart of signaling and disease
The ankyrin (ANK) repeat is one of the most common protein-protein interaction motifs in nature, a roughly 33-residue helix-turn-helix unit that stacks in tandem arrays to build elongated, curved…
- The Ras Superfamily of Small GTPases: Molecular Switches in Signalling, Traffic, and Disease
The Ras superfamily (Pfam PF00071) comprises small (~21 kDa) guanine-nucleotide-binding proteins that act as binary molecular switches, cycling between an active GTP-bound and an inactive GDP-bound…
- Pleckstrin homology domains: phosphoinositide-driven membrane targeting in PI3K signaling
The pleckstrin homology (PH) domain is a compact protein module that reads the lipid composition of cellular membranes, allowing signaling proteins to be recruited to specific bilayers in response to…
- EF-Hand Calcium-Binding Proteins: Structure, Mechanism, and Disease from Calmodulin to the Calcineurin and Ryanodine Receptor Axes
The EF-hand is the canonical helix-loop-helix motif through which cells decode intracellular Ca2+ signals into protein activity. Calmodulin (CaM) is the archetype, a small, dumbbell-shaped protein…
- Immunoglobulin V-set domains: variable receptors at the heart of immune recognition
The immunoglobulin V-set domain (Pfam PF07686) is the variable-type Ig fold that underpins antigen recognition and immune regulation. It defines the antigen-binding variable regions of antibodies and…
- Translational GTPases of the GTP_EFTU Family: Mechanism, Mimicry, and Modern Biology
The GTP_EFTU domain (Pfam PF00009) defines a family of translational GTPases that power and regulate every phase of protein synthesis. Members include the elongation factors EF-Tu (bacterial) and its…
- Globins and Hemoglobins: Oxygen Transport, Nitric Oxide Biology, and the Expanding Globin Family
The globin fold (Pfam PF00042) defines an ancient and functionally versatile protein family built around a single heme prosthetic group. Its canonical roles are the transport and storage of molecular…
- Serpins: the metastable architecture of the serine protease inhibitor superfamily, from mechanism to conformational disease
The serpins (serine protease inhibitors) are the predominant family of serine protease inhibitors in humans, and they regulate a remarkable breadth of physiology, including coagulation, fibrinolysis,…
- Carbonic anhydrases: structure, catalysis, and therapeutic targeting of the α-CA family
Carbonic anhydrases (CAs, EC 4.2.1.1) are zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. The α-class (Pfam PF00194) comprises a large family…