Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures

2013 ◽  
Vol 455 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Fei Ye ◽  
Mingjie Zhang
Keyword(s):  
Amino Acid ◽  
Pdz Domain ◽  
Binding Mode ◽  
Structural Features ◽  
Scaffold Proteins ◽  
Amino Acid Residues ◽  
Pdz Domains ◽  
Target Proteins ◽  
Protein Protein Interaction ◽  
Target Binding

PDZ domains are highly abundant protein–protein interaction modules and are often found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins regulate multiple biological processes, including trafficking and clustering receptors and ion channels at defined membrane regions, organizing and targeting signalling complexes at specific cellular compartments, interfacing cytoskeletal structures with membranes, and maintaining various cellular structures. PDZ domains, each with ~90-amino-acid residues folding into a highly similar structure, are best known to bind to short C-terminal tail peptides of their target proteins. A series of recent studies have revealed that, in addition to the canonical target-binding mode, many PDZ–target interactions involve amino acid residues beyond the regular PDZ domain fold, which we refer to as extensions. Such extension sequences often form an integral structural and functional unit with the attached PDZ domain, which is defined as a PDZ supramodule. Correspondingly, PDZ-domain-binding sequences from target proteins are frequently found to require extension sequences beyond canonical short C-terminal tail peptides. Formation of PDZ supramodules not only affords necessary binding specificities and affinities demanded by physiological functions of PDZ domain targets, but also provides regulatory switches to be built in the PDZ–target interactions. At the 20th anniversary of the discovery of PDZ domain proteins, we try to summarize structural features and target-binding properties of such PDZ supramodules emerging from studies in recent years.

scholarly journals Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia

2004 ◽  
Vol 200 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Bradley T. Messmer ◽  
Emilia Albesiano ◽  
Dimitar G. Efremov ◽  
Fabio Ghiotto ◽  
Steven L. Allen ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Structural Features ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Amino Acid Residues ◽  
Antigen Receptors ◽  
Region Gene ◽  
V Region ◽  
Unique Amino Acid

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.

scholarly journals The influence of sex steroid hormones on ferrochelatase gene expression in Harderian gland of hamster (Mesocricetus auratus)

2006 ◽  
Vol 189 (1) ◽  
pp. 103-112 ◽  
Author(s):  
F Vilchis ◽  
L Ramos ◽  
C Timossi ◽  
B Chávez
Keyword(s):  
Amino Acid ◽  
Steroid Hormones ◽  
Protoporphyrin Ix ◽  
Harderian Gland ◽  
Active Role ◽  
Structural Features ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Amino Acid Residues ◽  
Haem Proteins

Ferrochelatase (protohaem ferrolyase, EC 4.99.1.1), the terminal enzyme of the haem biosynthetic pathway, catalyses the insertion of ferrous iron into protoporphyrin IX to form protohaem. The Syrian hamster Harderian gland (HG) is known for its ability to produce and accumulate large amounts of protoporphyrins. In this species, the female gland contains up to 120 times more porphyrin than the male gland. Data from biochemical studies suggest that this gland possesses the enzymatic complex for haem biosynthesis but lacks ferrochelatase activity. The abundance of intraglandular haem proteins does not support this idea. To gain more insight into this process, we isolated cDNA for ferrochelatase from hamster liver, using the 5′- and 3′- rapid amplification of complementary DNA ends (RACE), and investigated its expression in HG from males and females. The full-length cDNA comprises an open reading frame of 1269 bp encoding a polypeptide of 422 amino-acid residues. Hamster DNA sequence exhibits 92% identity to mouse and 87% identity to human sequences. The predicted hamster enzyme was shown to have structural features of mammalian ferrochelatase, including a putative NH2- terminal presequence, a central core of about 330 amino-acid residues and an extra 30–50-amino-acid stretch at the carboxyl-terminus. RNA blotting experiments indicated that this cDNA hybridized to a liver mRNA of about 2.1 kb, while a weak hybridization signal was observed with mRNA from HG preparations. RT–PCR assays confirmed the expression of specific transcripts in both tissues. Male glands contained approximately twofold more enzyme mRNA than female glands. Likewise, the intraglandular content of mRNA varied during the oestrous cycle, with the highest levels found in the oestrous phase. These cyclic variations were less evident in liver. Ovariectomy plus treatment with progesterone or 17β-oestradiol plus progesterone increased ferrochelatase mRNA of the gland. In HG of short- or long-term castrated males, the administration of testosterone did not affect the ferrochelatase mRNA concentration. Based on mRNA expression levels, we conclude that Harderian ferrochelatase may play an active role in maintaining the physiological pool of haem required for processing cytochromes and other glandular haem proteins. Likewise, the sex-steroid hormones appear to have only a modest influence upon Harderian ferrochelatase.

scholarly journals Role of the PDZ Domains in Escherichia coli DegP Protein

2007 ◽  
Vol 189 (8) ◽  
pp. 3176-3186 ◽  
Author(s):  
Jack Iwanczyk ◽  
Daniela Damjanovic ◽  
Joel Kooistra ◽  
Vivian Leong ◽  
Ahmad Jomaa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protease Activity ◽  
Pdz Domain ◽  
Structural Features ◽  
Periplasmic Protein ◽  
Pdz Domains ◽  
Protease Domain ◽  
Interaction Domains ◽  
And Function

ABSTRACT PDZ domains are modular protein interaction domains that are present in metazoans and bacteria. These domains possess unique structural features that allow them to interact with the C-terminal residues of their ligands. The Escherichia coli essential periplasmic protein DegP contains two PDZ domains attached to the C-terminal end of the protease domain. In this study we examined the role of each PDZ domain in the protease and chaperone activities of this protein. Specifically, DegP mutants with either one or both PDZ domains deleted were generated and tested to determine their protease and chaperone activities, as well as their abilities to sequester unfolded substrates. We found that the PDZ domains in DegP have different roles; the PDZ1 domain is essential for protease activity and is responsible for recognizing and sequestering unfolded substrates through C-terminal tags, whereas the PDZ2 domain is mostly involved in maintaining the hexameric cage of DegP. Interestingly, neither of the PDZ domains was required for the chaperone activity of DegP. In addition, we found that the loops connecting the protease domain to PDZ1 and connecting PDZ1 to PDZ2 are also essential for the protease activity of the hexameric DegP protein. New insights into the roles of the PDZ domains in the structure and function of DegP are provided. These results imply that DegP recognizes substrate molecules targeted for degradation and substrate molecules targeted for refolding in different manners and suggest that the substrate recognition mechanisms may play a role in the protease-chaperone switch, dictating whether the substrate is degraded or refolded.

scholarly journals Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid β42 Anti-Aggregation Properties

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2125 ◽  
Author(s):  
Kazuma Murakami ◽  
Kazuhiro Irie
Keyword(s):  
Amino Acid ◽  
Functional Food ◽  
Structural Characteristics ◽  
Salt Bridge ◽  
Basic Amino Acid ◽  
Structural Features ◽  
Amino Acid Residues ◽  
Treatment And Prevention ◽  
Food Components ◽  
Underlying Mechanisms

Aggregation of amyloid β42 (Aβ42) is one of the hallmarks of Alzheimer’s disease (AD). There are numerous naturally occurring products that suppress the aggregation of Aβ42, but the underlying mechanisms remain to be elucidated. Based on NMR and MS spectroscopic analysis, we propose three structural characteristics found in natural products required for the suppressive activity against Aβ42 aggregation (i.e., oligomerization by targeting specific amino acid residues on this protein). These characteristics include (1) catechol-type flavonoids that can form Michael adducts with the side chains of Lys16 and 28 in monomeric Aβ42 through flavonoid autoxidation; (2) non-catechol-type flavonoids with planarity due to α,β-unsaturated carbonyl groups that can interact with the intermolecular β-sheet region in Aβ42 aggregates, especially aromatic rings such as those of Phe19 and 20; and (3) carboxy acid derivatives with triterpenoid or anthraquinoid that can generate a salt bridge with basic amino acid residues such as Lys16 and 28 in the Aβ42 dimer or trimer. Here, we summarize the recent body of knowledge concerning amyloidogenic inhibitors, particularly in functional food components and Kampo medicine, and discuss their application in the treatment and prevention of AD.

scholarly journals Human red blood cell Wright antigens: a genetic and evolutionary perspective on glycophorin A-band 3 interaction

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3942-3947 ◽  
Author(s):  
CH Huang ◽  
ME Reid ◽  
SS Xie ◽  
OO Blumenfeld
Keyword(s):  
Amino Acid ◽  
Nonhuman Primates ◽  
Antigen Expression ◽  
Band 3 ◽  
Structural Basis ◽  
Antigenic Structure ◽  
Glycophorin A ◽  
Amino Acid Residues ◽  
Protein Protein Interaction ◽  
Human Red Blood Cells

The Wright (Wra/Wrb) blood group polymorphism is defined by an allelic change (Lys658Glu) in the band 3 protein; nevertheless, the Wrb antigen apparently requires glycophorin A (GPA) for surface presentation. To gain insight into the structural basis for this protein-protein interaction and delineate its relationship with Wrb antigen expression, we investigated GPA and band 3 sequence polymorphisms occurring in rare humans and nonhuman primates. The lack of GPA or amino acid residues 59 through 71 of GPA results in the absence of Wrb from human red blood cells (RBCs) exhibiting the MkMk, En(a-), or MiV phenotype. However, the SAT homozygous cells carried a Glu658 form of band 3 and a hybrid glycophorin with the entire GPA extramembrane domain from residues 1 through 71, yet expressed no Wrb antigen. This finding suggests that formation of the Wrb antigenic structure is dependent on protein folding and that the transmembrane junction of GPA is important in maintaining the required conformation. Comparative analyses of GPA and band 3 homologues led to the identification in the interacting regions of conserved and dispensable amino acid residues that correlated with the Wrb positive or negative status on nonhuman primates. In particular, the chimpanzee RBCs cells expressed Wrb and the Glu658 form of band 3, which is identical to humans, but their GPA contained the Gly rather than Arg residue at position 61. Taken together, the results suggest that (1) Arg61 of GPA and the proposed Arg61-Glu658 charge pair are not crucial for Wrb antigen exhibition and (2) the role of GPA for interaction with band 3, including Glu658, probably involves a number of amino acid residues located in the alpha-helical region and transmembrane junction.

Foldamers containing γ-amino acid residues or their analogues: structural features and applications

Amino Acids ◽  
2011 ◽  
Vol 41 (3) ◽  
pp. 687-707 ◽  
Author(s):  
Francelin Bouillère ◽  
Sophie Thétiot-Laurent ◽  
Cyrille Kouklovsky ◽  
Valérie Alezra
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Amino Acid Residues

scholarly journals H-2Kd-restricted antigenic peptides share a simple binding motif.

1991 ◽  
Vol 174 (3) ◽  
pp. 603-612 ◽  
Author(s):  
P Romero ◽  
G Corradin ◽  
I F Luescher ◽  
J L Maryanski
Keyword(s):  
Amino Acid ◽  
Mhc Class I ◽  
Specific Binding ◽  
Structural Features ◽  
Class I ◽  
Binding Motif ◽  
Antigenic Peptides ◽  
Amino Acid Residues ◽  
Antigenic Activity ◽  
Mhc Class I Molecule

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.

Protein kinases in seeds

1998 ◽  
Vol 8 (2) ◽  
pp. 193-200 ◽  
Author(s):  
M. K. Walker-Simmons
Keyword(s):  
Amino Acid ◽  
Environmental Stress ◽  
Protein Phosphorylation ◽  
Protein Kinases ◽  
Protein Interaction ◽  
Stress Responses ◽  
Amino Acid Residues ◽  
Protein Protein Interaction ◽  
Reversible Protein Phosphorylation

AbstractReversible phosphorylation is catalysed by protein kinases that transfer the γ-phosphate from ATP to amino acid residues of proteins. The process can be reversed by protein phosphatases. Phosphorylation can dramatically activate or inhibit enzymes and affect protein-protein interaction. Through phosphorylation protein kinases can amplify and propagate cellular signals. In plants and now seeds, protein kinases involved in hormone, defence and environmental stress responses are being identified. Increasingly, these protein kinases are being cloned and characterized, demonstrating the major role of reversible protein phosphorylation in seeds.

The Shank family of scaffold proteins

2000 ◽  
Vol 113 (11) ◽  
pp. 1851-1856 ◽  
Author(s):  
M. Sheng ◽  
E. Kim
Keyword(s):  
Pdz Domain ◽  
Scaffold Proteins ◽  
Cell Junctions ◽  
Excitatory Synapses ◽  
Protein Protein Interaction ◽  
Sam Domain ◽  
New Family ◽  
Cytoplasmic Proteins ◽  
Specific Localization ◽  
G Protein Coupled

Shank proteins make up a new family of scaffold proteins recently identified through their interaction with a variety of membrane and cytoplasmic proteins. Shank polypeptides contain multiple sites for protein-protein interaction, including ankyrin repeats, an SH3 domain, a PDZ domain, a long proline-rich region, and a SAM domain. Binding partners for most of these domains have been identified: for instance, the PDZ domain of Shank proteins interacts with GKAP (a postsynaptic-density protein) as well as several G-protein-coupled receptors. The specific localization of Shank proteins at postsynaptic sites of brain excitatory synapses suggests a role for this family of proteins in the organization of cytoskeletal/ signaling complexes at specialized cell junctions.

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