Abstract:
:Early influences led me first to medical school with a view to microbiology, but I felt the lack of a deeper foundation and changed to chemistry, which in turn led me to physics and mathematics. I moved to the University of Cape Town to work on the X-ray crystallography of some small organic compounds. I developed a new method of using molecular structure factors to solve the crystal structure, which won me a research studentship to Trinity College Cambridge and the Cavendish Laboratory. There I worked on the austenite-pearlite transition in steel. This is governed by the dissipation of latent heat, and I ended up numerically solving partial differential equations. I used the idea of nucleation and growth during the phase change, which had its echo when I later tackled the assembly of Tobacco mosaic virus (TMV) from its constituent RNA and protein subunits. I wanted to move on to X-ray structure analysis of large biological molecules and obtained a Nuffield Fellowship to work in J.D. Bernal's department at Birkbeck College, London. There, I met Rosalind Franklin, who had taken up the study of TMV. I was able to interpret some of Franklin's beautiful X-ray diffraction patterns of the virus particle. From then on, my fate was sealed. After Franklin's untimely death in 1958, I moved in 1962 to the newly built MRC Laboratory of Molecular Biology in Cambridge, which, under Max Perutz, housed the original MRC unit from the Cavendish Laboratory. I was thus privileged to join the Laboratory at an early stage in its expansion and consequently able to take advantage of, and to help build up, its then unique environment of intellectual and technological sophistication. There I have remained ever since.
journal_name
Annu Rev Biochemjournal_title
Annual review of biochemistryauthors
Klug Adoi
10.1146/annurev.biochem.79.091407.093947subject
Has Abstractpub_date
2010-01-01 00:00:00pages
1-35eissn
0066-4154issn
1545-4509journal_volume
79pub_type
传,历史文章,杂志文章abstract::Microtubules are polymers that are essential for, among other functions, cell transport and cell division in all eukaryotes. The regulation of the microtubule system includes transcription of different tubulin isotypes, folding of /¿-tubulin heterodimers, post-translation modification of tubulin, and nucleotide-based ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.69.1.277
更新日期:2000-01-01 00:00:00
abstract::The base excision repair pathway is an organism's primary defense against mutations induced by oxidative, alkylating, and other DNA-damaging agents. This pathway is initiated by DNA glycosylases that excise the damaged base by cleavage of the glycosidic bond between the base and the DNA sugar-phosphate backbone. A sub...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.68.1.255
更新日期:1999-01-01 00:00:00
abstract::Sorting of transmembrane proteins to endosomes and lysosomes is mediated by signals present within the cytosolic domains of the proteins. Most signals consist of short, linear sequences of amino acid residues. Some signals are referred to as tyrosine-based sorting signals and conform to the NPXY or YXXO consensus moti...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.72.121801.161800
更新日期:2003-01-01 00:00:00
abstract::Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired profess...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-062917-012341
更新日期:2018-06-20 00:00:00
abstract::The structure and integrity of telomeres are essential for genome stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. The maintenance of telomere repeats in most eukaryotic organisms requires telomerase, which consists of a reverse transcriptase (RT) and an RNA te...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.75.103004.142412
更新日期:2006-01-01 00:00:00
abstract::Ryanodine receptors (RyRs)/Ca2+ release channels, on the endoplasmic and sarcoplasmic reticulum of most cell types, are required for intracellular Ca2+ release involved in diverse cellular functions, including muscle contraction and neurotransmitter release. The large cytoplasmic domain of the RyR serves as a scaffold...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.76.053105.094237
更新日期:2007-01-01 00:00:00
abstract::Multistep chemical reactions are increasingly seen as important in a growing number of complex biotransformations. Covalently attached prosthetic groups or swinging arms, and their associated protein domains, are essential to the mechanisms of active-site coupling and substrate channeling in a number of the multifunct...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.69.1.961
更新日期:2000-01-01 00:00:00
abstract::The protein kinase Akt/PKB is activated via a multistep process by a variety of signals. In the early steps of this process, PI-3 kinase-generated D3-phosphorylated phosphoinositides bind the Akt PH domain and induce the translocation of the kinase to the plasma membrane where it co-localizes with phosphoinositide-dep...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.68.1.965
更新日期:1999-01-01 00:00:00
abstract::Genetic, biochemical, and spectroscopic studies have established a new function for an intracellular protein, i.e., guiding and inserting a copper cofactor into the active site of a target enzyme. Studies of these new proteins have revealed a fundamental aspect of copper physiology, namely the vast overcapacity of the...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.70.1.677
更新日期:2001-01-01 00:00:00
abstract::SELEX is a technology for the identification of high affinity oligonucleotide ligands. Large libraries of random sequence single-stranded oligonucleotides, whether RNA or DNA, can be thought of conformationally not as short strings but rather as sequence dependent folded structures with high degrees of molecular rigid...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.64.070195.003555
更新日期:1995-01-01 00:00:00
abstract::Over the past three decades, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught with many challenges, today the field stands on firm foundations. Researchers now successfully retrieve nucleotide and amin...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-062917-012002
更新日期:2018-06-20 00:00:00
abstract::The packaging of chromosomal DNA by nucleosomes condenses and organizes the genome, but occludes many regulatory DNA elements. However, this constraint also allows nucleosomes and other chromatin components to actively participate in the regulation of transcription, chromosome segregation, DNA replication, and DNA rep...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.77.062706.153223
更新日期:2009-01-01 00:00:00
abstract::Mechanisms of chemical reaction can often be predicted by determining the dependence of the lifetime of reaction intermediates on the structure of the reactants. When there is no lifetime in the presence of another reactant or catalyst the reaction proceeds through an enforced concerted mechanism. Noncovalent binding ...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev.biochem.66.1.1
更新日期:1997-01-01 00:00:00
abstract::The assembly of individual proteins into functional complexes is fundamental to nearly all biological processes. In recent decades, many thousands of homomeric and heteromeric protein complex structures have been determined, greatly improving our understanding of the fundamental principles that control symmetric and a...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034142
更新日期:2015-01-01 00:00:00
abstract::This review focuses on eukaryotic translesion synthesis (TLS) DNA polymerases, and the emphasis is on Saccharomyces cerevisiae and human Y-family polymerases (Pols) eta, iota, kappa, and Rev1, as well as on Polzeta, which is a member of the B-family polymerases. The fidelity, mismatch extension ability, and lesion byp...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.74.082803.133250
更新日期:2005-01-01 00:00:00
abstract::Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of syst...
journal_title:Annual review of biochemistry
pub_type: 历史文章,杂志文章,评审
doi:10.1146/annurev-biochem-061516-045115
更新日期:2017-06-20 00:00:00
abstract::The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that th...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-080411-124036
更新日期:2014-01-01 00:00:00
abstract::DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication and escape proofreading. MMR proteins also participate in many other DNA transactions, such that inactivation of MMR can have wide-ranging biological consequences, which can be either beneficial o...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.74.082803.133243
更新日期:2005-01-01 00:00:00
abstract::Endocytic mechanisms control the lipid and protein composition of the plasma membrane, thereby regulating how cells interact with their environments. Here, we review what is known about mammalian endocytic mechanisms, with focus on the cellular proteins that control these events. We discuss the well-studied clathrin-m...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.78.081307.110540
更新日期:2009-01-01 00:00:00
abstract::Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized as precursors in the cytosol and are imported into mitochondria by five transport pathways. The protein import machineries of the mitochondrial membr...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060815-014352
更新日期:2017-06-20 00:00:00
abstract::Regulation of gene transcription is vitally important for the maintenance of normal cellular homeostasis. Failure to correctly regulate gene expression, or to deal with problems that arise during the transcription process, can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-052110-120012
更新日期:2012-01-01 00:00:00
abstract::Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease. Dominant mutations in the gene encoding alpha-synuclein enhance the propensity of this protein to aggregate. As a consequence, these patients have a widespread disease with protein inclusion bodies in several brain a...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.74.082803.133400
更新日期:2005-01-01 00:00:00
abstract::Proteins are increasingly used in basic and applied biomedical research. Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marg...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-062917-012102
更新日期:2018-06-20 00:00:00
abstract::Cys2His2 zinc finger proteins offer a stable and versatile framework for the design of proteins that recognize desired target sites on double-stranded DNA. Individual fingers from these proteins have a simple beta beta alpha structure that folds around a central zinc ion, and tandem sets of fingers can contact neighbo...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.70.1.313
更新日期:2001-01-01 00:00:00
abstract::My coworkers and I have used animal viruses and their interaction with host cells to investigate cellular processes difficult to study by other means. This approach has allowed us to branch out in many directions, including membrane protein characterization, endocytosis, secretion, protein folding, quality control, an...
journal_title:Annual review of biochemistry
pub_type: 杂志文章
doi:10.1146/annurev-biochem-011320-103928
更新日期:2020-06-20 00:00:00
abstract::Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of replication forks, for telomere maintenance, and chromosome segregation in meiosis I. As such, HR is indispensable for the main...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.77.061306.125255
更新日期:2008-01-01 00:00:00
abstract::Active transport between the nucleus and cytoplasm involves primarily three classes of macromolecules: substrates, adaptors, and receptors. Some transport substrates bind directly to an import or an export receptor while others require one or more adaptors to mediate formation of a receptor-substrate complex. Once ass...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.67.1.265
更新日期:1998-01-01 00:00:00
abstract::Aerobic life is possible because the molecular structure of oxygen (O2) makes direct reaction with most organic materials at ambient temperatures an exceptionally slow process. Of course, these reactions are inherently very favorable, and they occur rapidly with the release of a great deal of energy at high temperatur...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-013118-111529
更新日期:2019-06-20 00:00:00
abstract::The existence and function of actin in the nucleus has been hotly debated for forty years. Recently, beta-actin was found to be a component of mammalian SWI/SNF-like BAF chromatin remodeling complexes and still more recently other SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man. Although the fu...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.71.110601.135507
更新日期:2002-01-01 00:00:00
abstract::A broad view is given of photoregulated processes as they occur in algae, fungi, halophilic bacteria, higher plants, invertebrates, and higher animals. Emphasis is on the following: the organs, tissues, and organelles that participate; the nature of the photoreceptor pigments; the light-induced structural changes that...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.45.070176.001411
更新日期:1976-01-01 00:00:00