Biomedical subjects

Markus Gruber

Publications and source records attributed to Markus Gruber.

9 recordsLinked to original sources

PubMed2006

The HAMP domain structure implies helix rotation in transmembrane signaling.

HAMP domains connect extracellular sensory with intracellular signaling domains in over 7500 proteins, including histidine kinases, adenylyl cyclases, chemotaxis receptors, and phosphatases. The solution structure of an archaeal HAMP domain shows a homodimeric, four-helical, parallel coiled coil with unusual interhelical packing, related to the canonical packing by rotation of the helices. This suggests a model for the mechanism of signal transduction, in which HAMP alternates between the observed conformation and a canonical coiled coil. We explored this mechanism in vitro and in vivo using HAMP domain fusions with a mycobacterial adenylyl cyclase and an E. coli chemotaxis receptor. Structural and functional studies show that the equilibrium between the two forms is dependent on the side-chain size of residue 291, which is alanine in the wild-type protein.

Adenosine Triphosphate↗

PubMed2006

Direct corticospinal pathways contribute to neuromuscular control of perturbed stance.

The antigravity soleus muscle (Sol) is crucial for compensation of stance perturbation. A corticospinal contribution to the compensatory response of the Sol is under debate. The present study assessed spinal, corticospinal, and cortical excitability at the peaks of short- (SLR), medium- (MLR), and long-latency responses (LLR) after posterior translation of the feet. Transcranial magnetic stimulation (TMS) and peripheral nerve stimulation were individually adjusted so that the peaks of either motor evoked potential (MEP) or H reflex coincided with peaks of SLR, MLR, and LLR, respectively. The influence of specific, presumably direct, corticospinal pathways was investigated by H-reflex conditioning. When TMS was triggered so that the MEP arrived in the Sol at the same time as the peaks of SLR and MLR, EMG remained unaffected. Enhanced EMG was observed when the MEP coincided with the LLR peak (P < 0.001). Similarly, conditioning of the H reflex by subthreshold TMS facilitated H reflexes only at LLR (P < 0.001). The earliest facilitation after perturbation occurred after 86 ms. The TMS-induced H-reflex facilitation at LLR suggests that increased cortical excitability contributes to the augmentation of the LLR peaks. This provides evidence that the LLR in the Sol muscle is at least partly transcortical, involving direct corticospinal pathways. Additionally, these results demonstrate that approximately 86 ms after perturbation, postural compensatory responses are cortically mediated.

Adult↗

PubMed2006

Model structure of the prototypical non-fimbrial adhesin YadA of Yersinia enterocolitica.

Non-fimbrial adhesins, such as Yersinia YadA, Moraxella UspA1 and A2, Haemophilus Hia and Hsf, or Bartonella BadA represent an important class of molecules by which pathogenic proteobacteria adhere to their hosts. They form trimeric surface structures with a head-stalk-anchor architecture. Whereas head and stalk domains are diverse and appear (frequently repetitively) in different combinations, the anchor domains are homologous and display the properties of autotransporters. We have built a molecular model for the prototypical non-fimbrial adhesin, YadA, by combining the crystal structure of the head (PDB:1P9H) with theoretical models for the stalk and the anchor. The head domain is a single-stranded, left-handed beta-helix, connected to the stalk by a conserved trimerization element (the neck). The stalk consists of a right-handed coiled coil, containing ten 15-residue repeats with a C-terminal stutter (insertion of four residues). The stalk continues into the conserved anchor domain, which is formed by four heptads of a left-handed coiled coil, followed by four transmembrane beta-strands. Our model of the YadA coiled coil, generated with the program BeammotifCC, combines these periodicities into a structure that starts with a pronounced right-handed supercoil and ends with a canonical, left-handed conformation. The last two heptads of the coiled coil are located within a 12-stranded beta-barrel, formed by trimerization of the four transmembrane beta-strands in each monomer. We propose that this pore assembles in the outer membrane to form the opening through which the monomer chains exit the cell. After export is completed, the fiber folds and the pore is occluded by the coiled coil. Our model explains how these proteins can act as autotransporters in the absence of any homology to classical, single-chain autotransporters.

Adhesins, Bacterial↗

PubMed2006

Comparative analysis of coiled-coil prediction methods.

In this study we compare commonly used coiled-coil prediction methods against a database derived from proteins of known structure. We find that the two older programs COILS and PairCoil/MultiCoil are significantly outperformed by two recent developments: Marcoil, a program built on hidden Markov models, and PCOILS, a new COILS version that uses profiles as inputs; and to a lesser extent by a PairCoil update, PairCoil2. Overall Marcoil provides a slightly better performance over the reference database than PCOILS and is considerably faster, but it is sensitive to highly charged false positives, whereas the weighting option of PCOILS allows the identification of such sequences.

Amino Acid Sequence↗

PubMed2005

REPPER--repeats and their periodicities in fibrous proteins.

REPPER (REPeats and their PERiodicities) is an integrated server that detects and analyzes regions with short gapless repeats in protein sequences or alignments. It finds periodicities by Fourier Transform (FTwin) and internal similarity analysis (REPwin). FTwin assigns numerical values to amino acids that reflect certain properties, for instance hydrophobicity, and gives information on corresponding periodicities. REPwin uses self-alignments and displays repeats that reveal significant internal similarities. Both programs use a sliding window to ensure that different periodic regions within the same protein are detected independently. FTwin and REPwin are complemented by secondary structure prediction (PSIPRED) and coiled coil prediction (COILS), making the server a versatile analysis tool for sequences of fibrous proteins. REPPER is available at http://protevo.eb.tuebingen.mpg.de/repper.

Adhesins, Bacterial↗

PubMed2005

The structure of alpha-helical coiled coils.

alpha-Helical coiled coils are versatile protein domains, supporting a wide range of biological functions. Their fold is probably better understood than that of any other protein; indeed, uniquely among folds, their structure can be computed from a set of parametric equations. Here, we review the principles of coiled-coil structure, the determinants of their folding and stability, and the diversity of structural forms they assume.

Animals↗

PubMed2004

Impact of sensorimotor training on the rate of force development and neural activation.

The ability to generate high muscular strength within short time periods is of functional importance not only as a basic quality in many sports disciplines but also for active stabilization of joints. The rate of force development (RFD) is generally used to describe this ability. The purpose of the present study was to examine the functional adaptations of a specific sensorimotor training on the explosive strength qualities of the leg extensor muscles during maximum isometric actions. Force and surface EMG were recorded in 17 subjects before and after a 4-week sensorimotor training period. Maximum static leg press strength did not change [608.2 (47.0) N to 627.8 (48.4) N before/after training], whereas maximum RFD (RFD(max)) increased significantly from 4.95 (0.48) N/ms to 6.58 (0.76) N/ms (P<0.05). The gain in RFD(max) was accompanied by an increased EMG of the M. vastus medialis. Enhancement of neuromuscular activation was only prominent in the early phases of muscular action. Neither force nor EMG parameters revealed significant improvements for time phases beyond 100 ms following the onset of isometric action. Enhanced extrafacilitatory drive from the afferent system is discussed as a potential mechanism for the improved neural activation. From a more functional point of view, this type of adaptation may be helpful in various sport performances. Moreover, with regard to injury related situations, enhanced neuromuscular activation is of distinct relevance in order to stiffen joint complexes actively within short time periods.

Adaptation, Physiological↗

PubMed2004

Coiled coils meet the chaperone world.

Coiled coils are versatile structural modules that engage in a variety of cellular activities. Recent studies illuminate their role as substrate-binding elements in the chaperone cofactor prefoldin and in the AAA+ ATPases involved in protein (un)folding processes. The use of coiled coils to mediate the binding of non-native proteins represents a novel strategy in chaperone design and a new function for coiled coils.

Adenosine Triphosphatases↗

PubMed2003

Historical review: another 50th anniversary--new periodicities in coiled coils.

In 1953, Francis Crick and Linus Pauling both proposed models of supercoiled alpha helices ('coiled coils') for the structure of keratin. These were the first attempts at modelling the tertiary structure of a protein. Crick emphasized the packing mode of the side-chains ('knobs-into-holes'), which required a periodicity of seven residues over two helical turns (7/2) and a supercoil in the opposite sense of the constituent helices. By contrast, Pauling envisaged a broader set of periodicities (4/1, 7/2, 18/5, 15/4, 11/3) and supercoils of both senses. Crick's model became canonical and the 'heptad repeat' essentially synonymous with coiled coils, but 50 years later new crystal structures and protein sequences show that the less common periodicities envisaged by Pauling also occur in coiled coils, adding a variant packing mode ('knobs-to-knobs') to the standard model. Pauling's laboratory notebooks suggest that he searched unsuccessfully for this packing mode in 1953.

Amino Acid Motifs↗