Interaction between very-KIND Ras guanine exchange factor and microtubule-associated protein 2, and its role in dendrite growth – structure and function of the second kinase noncatalytic C-lobe domain Jinhong Huang 1, *, Asako Furuya 1 , Kanehiro Hayashi 1–3 and Teiichi Furuichi 1,2,4 1 Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Saitama, Japan 2 JST, CREST, Kawaguchi, Saitama, Japan 3 Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan 4 Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan Keywords dendrite growth; KIND domain; MAP2; protein–protein interaction; RasGEF Correspondence T. Furuichi, Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako 351-0198, Japan Fax: +81 48 467 6079 Tel: +81 48 467 5906 E-mail: tfuruichi@brain.riken.jp *Present address Discovery & Development Laboratory I, Hanno Research Center, Taiho Pharmaceutical Co., Ltd, Saitama, Japan (Received 5 January 2011, revised 19 February 2011, accepted 28 February 2011) doi:10.1111/j.1742-4658.2011.08085.x The kinase noncatalytic C-lobe domain (KIND) is a putative protein–protein interaction module. Four KIND-containing proteins, Spir-2 (actin-nuclear factor), PTPN13 (protein tyrosine phosphatase), FRMPD2 (scaffold protein) and very-KIND (v-KIND) (brain-specific Ras guanine nucleotide exchange factor), have been identified to date. Uniquely, v-KIND has two KINDs (i.e. KIND1 and KIND2), whereas the other three proteins have only one. The functional role of KIND, however, remains unclear. We previously demon- strated that v-KIND interacts with the high-molecular weight microtubule- associated protein 2 (MAP2), a dendritic microtubule-associated protein, leading to negative regulation of neuronal dendrite growth. In the present study, we analyzed the structure–function relationships of the v-KIND– MAP2 interaction by generating a series of mutant constructs. The interac- tion with endogenous MAP2 in mouse cerebellar granule cells was specific to v-KIND KIND2, but not KIND1, and was not observed for the KINDs from other KIND-containing proteins. The binding core modules critical for the v-KIND–MAP2 interaction were defined within 32 residues of the mouse v-KIND KIND2 and 43 residues of the mouse MAP2 central domain. Three Leu residues at amino acid positions 461, 474 and 477 in the MAP2-binding core module of KIND2 contributed to the interaction. The MAP2-binding core module itself promoted dendrite branching as a dominant-negative regu- lator of v-KIND in hippocampal neurons. The results reported in the present study demonstrate the structural and functional determinant underlying the v-KIND–MAP2 interaction that controls dendrite arborization patterns. Structured digital abstract l vKIND-KIND2 binds to Map2 by pull down (View interaction) l Map2 physically interacts with vKIND-KIND2 by pull down (View interaction 1, 2, 3, 4, 5) l Map2 physically interacts with vKIND by pull down (View interaction) l Map2 physically i nteracts with vKIND-KIND2 by anti bai t co immunoprecipitation (View i nteraction) l vKIND-KIND2 physically interacts with Map2 by pull down (View interaction) Abbreviations CD, central domain; DIV, day in vitro; EGFP, enhanced green fluorescent protein; GST, glutathione S-transferase; HMW, high-molecular- weight; KIND, kinase noncatalytic C-lobe domain; KIND1, first kinase Basic Structure and Function of the Nervous System Basic Structure and Function of the Nervous System Bởi: OpenStaxCollege The picture you have in your mind of the nervous system probably includes the brain, the nervous tissue contained within the cranium, and the spinal cord, the extension of nervous tissue within the vertebral column That suggests it is made of two organs—and you may not even think of the spinal cord as an organ—but the nervous system is a very complex structure Within the brain, many different and separate regions are responsible for many different and separate functions It is as if the nervous system is composed of many organs that all look similar and can only be differentiated using tools such as the microscope or electrophysiology In comparison, it is easy to see that the stomach is different than the esophagus or the liver, so you can imagine the digestive system as a collection of specific organs The Central and Peripheral Nervous Systems The nervous system can be divided into two major regions: the central and peripheral nervous systems The central nervous system (CNS) is the brain and spinal cord, and the peripheral nervous system (PNS) is everything else ([link]) The brain is contained within the cranial cavity of the skull, and the spinal cord is contained within the vertebral cavity of the vertebral column It is a bit of an oversimplification to say that the CNS is what is inside these two cavities and the peripheral nervous system is outside of them, but that is one way to start to think about it In actuality, there are some elements of the peripheral nervous system that are within the cranial or vertebral cavities The peripheral nervous system is so named because it is on the periphery—meaning beyond the brain and spinal cord Depending on different aspects of the nervous system, the dividing line between central and peripheral is not necessarily universal 1/13 Basic Structure and Function of the Nervous System Central and Peripheral Nervous System The structures of the PNS are referred to as ganglia and nerves, which can be seen as distinct structures The equivalent structures in the CNS are not obvious from this overall perspective and are best examined in prepared tissue under the microscope Nervous tissue, present in both the CNS and PNS, contains two basic types of cells: neurons and glial cells A glial cell is one of a variety of cells that provide a framework of tissue that supports the neurons and their activities The neuron is the more functionally important of the two, in terms of the communicative function of the nervous system To describe the functional divisions of the nervous system, it is important to understand the structure of a neuron Neurons are cells and therefore have a soma, or cell body, but they also have extensions of the cell; each extension is generally referred to as a process There is one important process that every neuron has called an axon, which is the fiber that connects a neuron with its target Another type of process that branches off from the soma is the dendrite Dendrites are responsible for receiving most of the input from other neurons Looking at nervous tissue, there are regions that predominantly contain cell bodies and regions that are largely composed of just axons These two regions within nervous system structures are often referred to as gray matter (the regions with many cell bodies and dendrites) or white matter (the regions with many axons) [link] demonstrates the appearance of these regions in the brain and spinal cord The colors ascribed to these regions are what would be seen in “fresh,” or unstained, nervous tissue Gray matter is not necessarily gray It can be pinkish because of blood content, or even slightly tan, depending on how long the tissue has been preserved But white matter is white because axons are insulated by a lipid-rich substance called myelin Lipids can appear as white (“fatty”) material, much like the fat on a raw piece of chicken or beef Actually, gray matter may have that color ascribed to it because next to the white matter, it is just darker—hence, gray 2/13 Basic Structure and Function of the Nervous System The distinction between gray matter and white matter is most often applied to central nervous tissue, which has large regions that can be seen with the unaided eye When looking at peripheral structures, often a microscope is used and the tissue is stained with artificial colors That is not to say that central nervous tissue cannot be stained and viewed under a microscope, but unstained tissue is most likely from the CNS—for example, a frontal section of the brain or cross section of the spinal cord Gray Matter and White Matter A brain removed during an autopsy, with a partial section removed, shows white matter surrounded by gray matter Gray matter makes up the outer cortex of the brain (credit: modification of work by “Suseno”/Wikimedia Commons) Regardless of the appearance of stained or unstained ... This page intentionally left blank Body Size: The Structure and Function of Aquatic Ecosystems Ecologists have long struggled to predict features of ecological systems, such as the numbers and diversity of organisms. The wide range of body sizes in ecological communities, from tiny microbes to large animals and plants, is emerging as the key to prediction. Based on the relationship of body size with key biological rates and with the physical world experienced by aquatic organisms, we may be able to understand patterns of abundance and diversity, biogeography, interactions in food webs and the impact of fishing, adding up to a potential ‘periodic table’ for ecology. Remarkable progress on the unravelling, describing and modelling of aquatic food webs, revealing the fundamental role of body size, makes a book emphasizing marine and freshwater ecosystems particularly apt. Here, the importance of body size is examined at a range of scales, yielding broad perspectives that will be of interest to professional ecologists, from students to senior researchers. A LAN G. HILDREW is Professor of Ecology in the School of Biological and Chemical Sciences at Queen Mary, University of London. D AVID G. RAFFAELLI is Professor of Environmental Science at the University of York. R ONNI E DMONDS-BROWN is a Senior Lecturer in Environmental Sciences at the University of Hertfordshire. Body Size The Structure and Function of Aquatic Ecosystems Edited by ALAN G. HILDREW School of Biological and Chemical Sciences, Queen Mary, University of London, UK DAVID G. RAFFAELLI Environment Department, University of York, UK RONNI EDMONDS-BROWN Division of Geography and Environmental Sciences, University of Hertfordshire, UK CAMBRIDGE UNIVERSITY PRESS Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK First published in print format ISBN-13 978-0-521-86172-4 ISBN-13 978-0-521-67967-1 ISBN-13 978-0-511-29508-9 © British Ecological Society 2007 2007 Information on this title: www.cambridge.org/9780521861724 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written p ermission of Cambrid g e University Press. ISBN-10 0-511-29508-1 ISBN-10 0-521-86172-1 ISBN-10 0-521-67967-2 Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not g uarantee that any content on such websites is, or will remain, accurate or a pp ro p riate. Published in the United States of America by Cambridge University Press, New York www.cambridge.org hardback paperback paperback eBook (EBL) eBook (EBL) hardback Contents List of contributors page vii Preface ix 1 The metabolic theory of ecology and the role of body size in marine and freshwater ecosystems James H. Brown, Andrew P. Allen and James F. Gillooly 1 2 Body size and suspension feeding Stuart Humphries 16 3 Life histories and body size David Atkinson and Andrew G. Hirst 33 4 Relationship between biomass turnover and body size for stream communities Alexander D. Huryn and Arthur C. Benke 55 5 Body size in streams: macroinvertebrate community size composition along natural and human-induced environmental gradients NMR solution structure and function of the C-terminal domain of eukaryotic class 1 polypeptide chain release factor Alexey B. Mantsyzov 1 , Elena V. Ivanova 2 , Berry Birdsall 3 , Elena Z. Alkalaeva 2 , Polina N. Kryuchkova 2,4 , Geoff Kelly 5 , Ludmila Y. Frolova 2 and Vladimir I. Polshakov 1 1 Center for Magnetic Tomography and Spectroscopy, M. V. Lomonosov Moscow State University, Russia 2 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 3 Division of Molecular Structure, MRC National Institute for Medical Research, London, UK 4 Chemical Department, M. V. Lomonosov Moscow State University, Russia 5 MRC Biomedical NMR Centre, NIMR, London, UK Keywords human eukaryotic class 1 polypeptide chain release factor (eRF1); NMR structure and dynamics; stop codon recognition specificity; termination of protein synthesis Correspondence V. I. Polshakov, Center for Magnetic Tomography and Spectroscopy, M. V. Lomonosov Moscow State University, GSP-1, Moscow, 119991, Russia Fax: +7 495 9394210 Tel: +7 495 9394882 E-mail: vpolsha@mail.ru Database The 1 H, 15 N and 13 C chemical shifts have been deposited in the BioMagResBank database (http://www.bmrb.wisc.edu) under the accession number BMRB-15366. The structural data and experimental restraints used in calculations have been submitted to the Protein Data Bank under the accession numbers 2KTV for the open conformer and 2KTU for the closed conformer Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://www3.interscience.wiley. com/authorresources/onlineopen.html (Received 17 December 2009, revised 1 April 2010, accepted 8 April 2010) doi:10.1111/j.1742-4658.2010.07672.x Termination of translation in eukaryotes is triggered by two polypeptide chain release factors, eukaryotic class 1 polypeptide chain release factor (eRF1) and eukaryotic class 2 polypeptide chain release factor 3. eRF1 is a three-domain protein that interacts with eukaryotic class 2 polypeptide chain release factor 3 via its C-terminal domain (C-domain). The high-reso- lution NMR structure of the human C-domain (residues 277–437) has been determined in solution. The overall fold and the structure of the b-strand core of the protein in solution are similar to those found in the crystal structure. The structure of the minidomain (residues 329–372), which was ill-defined in the crystal structure, has been determined in solution. The protein backbone dynamics, studied using 15 N-relaxation experiments, showed that the C-terminal tail 414–437 and the minidomain are the most flexible parts of the human C-domain. The minidomain exists in solution in two conformational states, slowly interconverting on the NMR time- scale. Superposition of this NMR solution structure of the human C-domain onto the available crystal structure of full-length human eRF1 shows that the minidomain is close to the stop codon-recognizing N-termi- nal domain. Mutations in the tip of the minidomain were found to affect the stop codon specificity of the factor. The results provide new insights into the possible role of the C-domain in the process of translation termi- nation. Abbreviations C-domain, C-terminal domain (or Structure and function of the 3-carboxy-cis,cis-muconate lactonizing enzyme from the protocatechuate degradative pathway of Agrobacterium radiobacter S2 Sad Halak 1, *, Lari Lehtio ¨ 2,3, *, Tamara Basta 1,† , Sibylle Bu ¨ rger 1 , Matthias Contzen 1,‡ , Andreas Stolz 1 and Adrian Goldman 2 1 Institut fu ¨ r Mikrobiologie, Universita ¨ t Stuttgart, Germany 2 Institute of Biotechnology, University of Helsinki, Finland 3 National Graduate School in Informational and Structural Biology, A ˚ bo Akademi University, Finland Keywords Agrobacterium; b-ketoadipate pathway; 3-carboxy-cis,cis-muconate lactonizing enzyme; fumarase II family Correspondence A. Goldman, Institute of Biotechnology, University of Helsinki, PO Box 65, 00014 HY, Finland Fax: +358 9 191 59940 Tel: +358 9 191 58923 E-mail: adrian.goldman@helsinki.fi A. Stolz, Institut fu ¨ r Mikrobiologie, Universita ¨ t Stuttgart, Allmandring 31, 70569 Stuttgart, Germany Fax: +49 711 685 6 5725 Tel: +49 711 685 6 5489 E-mail: andreas.stolz@imb.uni-stuttgart.de *These authors contributed equally to this work Present address † Institut Pasteur, Paris, France ‡ Chemisches und Veterina ¨ runtersuchungsamt Stuttgart, Fellbach, Germany (Received 8 August 2006, revised 22 Sep- tember 2006, accepted 25 September 2006) doi:10.1111/j.1742-4658.2006.05512.x 3-carboxy-cis,cis-muconate lactonizing enzymes participate in the protoca- techuate branch of the 3-oxoadipate pathway of various aerobic bacteria. The gene encoding a 3-carboxy-cis,cis-muconate lactonizing enzyme (pcaB1S2) was cloned from a gene cluster involved in protocatechuate deg- radation by Agrobacterium radiobacter strain S2. This gene encoded for a 3-carboxy-cis,cis-muconate lactonizing enzyme of 353 amino acids ) signifi- cantly smaller than all previously studied 3-carboxy-cis,cis-muconate lact- onizing enzymes. This enzyme, ArCMLE1, was produced in Escherichia coli and shown to convert not only 3-carboxy-cis,cis-muconate but also 3-sulfomuconate. ArCMLE1 was purified as a His-tagged enzyme variant, and the basic catalytic constants for the conversion of 3-carboxy-cis,cis- muconate and 3-sulfomuconate were determined. In contrast, Agrobacteri- um tumefaciens 3-carboxy-cis,cis-muconate lactonizing enzyme 1 could not, despite 87% sequence identity to ArCMLE1, use 3-sulfomuconate as sub- strate. The crystal structure of ArCMLE1 was determined at 2.2 A ˚ resolu- tion. Consistent with the sequence, it showed that the C-terminal domain, present in all other members of the fumarase II family, is missing in ArCMLE1. Nonetheless, both the tertiary and quaternary structures, and the structure of the active site, are similar to those of Pseudomonas putida 3-carboxy-cis,cis-muconate lactonizing enzyme. One principal difference is that ArCMLE1 contains an Arg, as opposed to a Trp, in the active site. This indicates that activation of the carboxylic nucleophile by a hydropho- bic environment is not required for lactonization, unlike earlier proposals [Yang J, Wang Y, Woolridge EM, Arora V, Petsko GA, Kozarich JW & Ringe D (2004) Biochemistry 43, 10424–10434]. We identified citrate and isocitrate as noncompetitive inhibitors of ArCMLE1, and found a potential binding pocket for them on the enzyme outside the active site. Abbreviations ArCMLE1, 3-carboxy-cis,cis-muconate lactonizing enzyme from Agrobacterium radiobacter strain S2; AtCMLE1, 3-carboxy-cis,cis-muconate lactonizing enzyme from Agrobacterium tumefaciens; 3CM, [...]... representative sample of actual use of the Arabic language As such, not only do we examine the text, but we also relate the verbal form to its context of use In addition, we pay close attention to the modal dimension, reminiscent of writers’ opinions and attitudes toward the propositional content At the heart of the Arabic verbal system, and most other verbal systems, are the issues of Aspect, Tense, and Modality... representations, on the one hand, and their semantic interpretations, on the other hand 7 VERBAL FORMS, CLAUSES, AND METHODOLOGY This chapter focuses, in particular, on the status and characteristics of these verbal categories, elements of a chief component Its objective is twofold: to reveal, first, the formal/structural properties of the verbal categories, and then to investigate their major inherent... Modality (ATM) These verbal categories appear to have puzzled every single relevant research for a number of reasons at the forefront of which might figure (i) the morphological opacity of the Arabic verb, (ii) the mixing of various historical eras of the Arabic language, and (iii) the absolute lack of authentic texts It is our strong belief that, with the current state of linguistic theory, it is hard... through showing the extent to which semantic structures are mapped into syntactic representations The language and the data The form of Arabic under investigation is Standard Arabic (henceforth Arabic) , also known as Modern Standard Arabic (MSA), and Modern Literary Arabic (MLA) It is the uniform variety of Arabic which is used all over the Arabic- speaking world as the usual medium of written communication... investigate the semantic–pragmatic functions of the second member of the opposition within the verbal system, namely the Imperfect These functions are traced out from the perspective of temporality Here, an effort is made to sort out the major contextual variants of this verbal form These variants are then hierarchically ... the central and peripheral nervous systems 10/13 Basic Structure and Function of the Nervous System The CNS is the brain and spinal cord The PNS is everything else Functionally, the nervous system. .. functionally important of the two, in terms of the communicative function of the nervous system To describe the functional divisions of the nervous system, it is important to understand the structure. . .Basic Structure and Function of the Nervous System Central and Peripheral Nervous System The structures of the PNS are referred to as ganglia and nerves, which can be seen as distinct structures