Structure and function of antifreeze proteins

High-resolution three-dimensional structures are now available for four of seven non-homologous fish and insect antifreeze proteins (AFPs). For each of these structures, the ice-binding site of the AFP has been defined by site-directed mutagenesis, and ice etching has indicated that the ice surface is bound by the AFP. A comparison of these extremely diverse ice-binding proteins shows that they have the following attributes in common. The binding sites are relatively flat and engage a substantial proportion of the protein's surface area in ice binding. They are also somewhat hydrophobic -- more so than that portion of the protein exposed to the solvent. Surface-surface complementarity appears to be the key to tight binding in which the contribution of hydrogen bonding seems to be secondary to van der Waals contacts.     

Structure and function of argonaute proteins

Argonaute (Ago) family proteins are multidomain proteins expressed in prokaryotic and eukaryotic organisms. In eukaryotes, Ago proteins are most well known for their roles in RNA silencing. In prokaryotes, the functions of Ago proteins are unknown, but based on their similarity to eukaryotic Ago proteins, they could be involved in nucleic acid-directed regulatory pathways related to RNA silencing. Recent structural and biochemical studies have shed new light on the function of this family of proteins. These studies reveal how these proteins recognize and cleave RNA and suggest a function for prokaryotic family members.     

Structure and function of Toll-like receptor proteins

Beginning in 1997 with the identification of the first human homologue of the Drosophila protein Toll, a family of related molecules have been identified in both humans and other mammals. These Toll-like receptor (TLR) proteins appear to represent a conserved family of innate immune recognition receptors. TLR proteins share extended homology with receptors for the cytokines interleukin 1 (IL-1) and interleukin 18 (IL-18). These receptors are coupled to a signaling pathway that is conserved in mammals, insects, and plants, resulting in cellular activation, thereby stimulating innate immune defenses. A variety of bacterial and fungal products have been identified that serve as TLR ligands, and more recent studies have identified the first endogenous protein ligands for TLR proteins. While TLR signaling is likely to be a key feature of innate immune responses, these proteins may also regulate homeostasis via interaction with endogenous protein ligands.     

Structure and function of mismatch repair proteins

DNA mismatch repair is required for maintaining genomic stability and is highly conserved from prokaryotes to eukaryotes. Errors made during DNA replication, such as deletions, insertions and mismatched basepairs, are substrates for mismatch repair. Mismatch repair is strand-specific and targets only the newly synthesized daughter strand. To initiate mismatch repair in Escherichia coli, three proteins are essential, MutS, for mismatch recognition, MutH, for introduction of a nick in the target strand, and MutL, for mediating the interactions between MutH and MutS. Homologues of MutS and MutL important for mismatch repair have been found in nearly all organisms. Mutations in MutS and MutL homologues have been linked to increased cancer susceptibility in both mice and humans. Here, we review the crystal structures of the MutH endonuclease, a conserved ATPase fragment of MutL (LN40), and complexes of LN40 with various nucleotides. Based on the crystal structure, the active site of MutH has been identified and an evolutionary relationship between MutH and type II restriction endonucleases established. Recent crystallographic and biochemical studies have revealed that MutL operates as a molecular switch with its interactions with MutH and MutS regulated by ATP binding and hydrolysis. These crystal structures also shed light on the general mechanism of mismatch repair and the roles of Mut proteins in preventing mutagenesis.     

Structure and function of SNARE and SNARE-interacting proteins

This review focuses on the so-called SNARE (soluble N-ethyl maleimide sensitive factor attachment protein receptor) proteins that are involved in exocytosis at the pre-synpatic plasma membrane. SNAREs play a role in docking and fusion of synaptic vesicles to the active zone, as well as in the Ca2+-triggering step itself, most likely in combination with the Ca2+ sensor synaptotagmin. Different SNARE domains are involved in different processes, such as regulation, docking, and fusion. SNAREs exhibit multiple configurational, conformational, and oliogomeric states. These different states allow SNAREs to interact with their matching SNARE partners, auxiliary proteins, or with other SNARE domains, often in a mutually exclusive fashion. SNARE core domains undergo progressive disorder to order transitions upon interactions with other proteins, culminating with the fully folded post-fusion (cis) SNARE complex. Physiological concentrations of neuronal SNAREs can juxtapose membranes, and promote fusion in vitro under certain conditions. However, significantly more work will be required to reconstitute an in vitro system that faithfully mimics the Ca2+-triggered fusion of a synaptic vesicle at the active zone.     

Structure, function and evolution of multidomain proteins

Proteins are composed of evolutionary units called domains; the majority of proteins consist of at least two domains. These domains and nature of their interactions determine the function of the protein. The roles that combinations of domains play in the formation of the protein repertoire have been found by analysis of domain assignments to genome sequences. Additional findings on the geometry of domains have been gained from examination of three-dimensional protein structures. Future work will require a domain-centric functional classification scheme and efforts to determine structures of domain combinations.     

Structure and function of WD40 domain proteins

The WD40 domain exhibits a β-propeller architecture, often comprising seven blades. The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes. In this review, we will discuss the identification, definition and architecture of the WD40 domains. WD40 domain proteins are involved in a large variety of cellular processes, in which WD40 domains function as a protein-protein or protein-DNA interaction platform. WD40 domain mediates molecular recognition events mainly through the smaller top surface, but also through the bottom surface and sides. So far, no WD40 domain has been found to display enzymatic activity. We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins. In the last part of this review, we will discuss how post-translational modifications are recognized by WD40 domain proteins.     

Structure and function of cytoplasmic retinoid binding proteins

We examined the ligand protein interactions of two highly homologous cellular retinol binding proteins, CRBP and CRBP-II, and two highly homologous cellular retinoic acid binding proteins, CRABP-I and CRABP-II. While the crystal structures of all four have been determined, nuclear magnetic resonance studies provide a means for observing dynamic aspects of ligand protein interactions of these proteins in solution. The cellular functions of these proteins are less well understood. We have modeled retinoid flux between cytoplasmic retinoid proteins and model membranes and with nuclear receptors. Based on our in vitro studies, we propose that certain retinoids may indirectly influence retinoid signaling by displacing endogenous retinoids from the cytoplasmic proteins to the nuclear receptors.     

哺乳动物中Kelch超家族蛋白的结构与功能

在不同生物体,如病毒、植物、真菌和哺乳动物中,几百种含Kelch构象的蛋白质已经被鉴定出来了,但大部分此类蛋白质的功能未知.而在哺乳动物中,已经有接近41种Kelch蛋白被报道.这些蛋白质在体内参与了很多重要的生理过程.根据Kelch蛋白的域结构不同,把这些哺乳动物中的Kelch蛋白分成了三类(BTB/Kelch蛋白,只含有Kelch结构域的蛋白质,及含其他结构域的Kelch蛋白),并把其已知的功能大致划分为5类:介导蛋白质-蛋白质的相互作用、参与蛋白质降解、信号传导、胞外功能及其他等.另外还认为Keap 1的Kelch结构域其晶体结构应该是研究哺乳动物Kelch蛋白的一个很好的参考模型.     

Structure and function of proteins in membranes and nanodiscs

The field of membrane structural biology represents a fast-moving field with exciting developments including native nanodiscs that allow preparation of complexes of post-translationally modified proteins bound to biological lipids. This has led to conceptual advances including biological membrane:protein assemblies or “memteins” as the fundamental functional units of biological membranes. Tools including cryo-electron microscopy and X-ray crystallography are maturing such that it is becoming increasingly feasible to solve structures of large, multicomponent complexes, while complementary methods including nuclear magnetic resonance spectroscopy yield unique insights into interactions and dynamics. Challenges remain, including elucidating exactly how lipids and ligands are recognized at atomic resolution and transduce signals across asymmetric bilayers. In this special volume some of the latest thinking and methods are gathered through the analysis of a range of transmembrane targets. Ongoing work on areas including polymer design, protein labelling and microfluidic technologies will ensure continued progress on improving resolution and throughput, providing deeper understanding of this most important group of targets.     

Structure and mechanisms of function of visual system proteins

Recent progress in understanding visual signal transduction in retinal cells is summarized. The roles of particular proteins in activation, amplification and termination of the photoresponse are described. Detailed information on the structure and function of the photoreceptor protein rhodopsin is presented. The latest data on visual pigment sequences, rhodopsin mutations in the autosomal-dominant retinitis pigmentosa, and the results of site-directed mutagenesis of the rhodopsin molecule are summarized.     

Structure and function of proteins involved in milk allergies

Allergy to milk proteins has been defined as any adverse reaction mediated by immunological mechanisms to one or several of proteins found in milk. The milk allergy has been classified according to the onset of symptoms as immediate or delayed type. The milk allergy seems to be manifested by three major proteins found in milk: α-lactalbumin, β-lactoglobulin and caseins. The structural comparison of allergenic sites in α-lactalbumin and β-lactoglobulin with the structure of lactoferrin has clearly shown that yet another major milk protein lactoferrin also possesses allergenic sites and thus may qualify to be an allergen. The heat treatment of milk proteins considerably reduces their allergenicity.