Structure of Lyme Disease Protein Determined

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Structure of Lyme Disease Protein Determined

(June 19, 2002) -- Scientists have determined the structure of a

telltale protein in the Lyme disease bacterium that picks a fight with a

patient's immune system and then evades the antibodies sent out to

destroy it.

Writing in the June 14 edition of the Journal of Biological Chemistry

(JBC), a team of researchers from The Texas A & M University System Health

Science Center Institute of Biosciences and Technology (IBT) in Houston,

Texas A & M University (TAMU) and The University of Texas Health Science

Center at Houston (UT-Houston) describe the protein's structure and

likely reasons for its ability to simultaneously provoke and dodge an

immune response.

Research on the protein has provided a highly accurate avenue for

diagnosing the disease, which can be difficult to recognize in many

cases, said co-senior author J. Norris, Ph.D., professor of

pathology and laboratory medicine at the UT-Houston Medical School.

Findings also explain in part the tenacity of Lyme disease, which can

survive in a host for years if left untreated.

The protein, known as VlsE, is found on the surface of the bacterium.

Six regions of the protein do not change as the organism multiplies,

while the genetics of six

other regions change rapidly and significantly. Using X-ray

crystallography, the research team at the Center for Structural Biology

at IBT and TAMU, led by C. Sacchettini, Ph.D., obtained a detailed

structure of the VlsE protein. Sacchettini is professor of biochemistry

and biophysics and of chemistry at Texas A & M University, holding the

Wolfe-Welch Chair in Science. He is also the director of the Center for

Structural Biology at Texas A & M and IBT.

The structure helps determine the precise location in the protein of the

variable and invariant portions. This offers important clues as to why

the antibodies against the

invariant regions are ineffective despite eliciting a strong immune

response in more than 90 percent of Lyme disease patients.

The JBC paper showed that the invariant regions are almost completely

buried within the protein and are largely inaccessible to antibodies.

The six variable regions,

on the other hand, lie mainly on the surface and mask the invariant

regions from the host defense. These changing areas may allow Lyme

disease to stay a step

ahead of the host's defenses by confounding the ability of antibodies to

bind to VlsE and hence destroy the bacterium.

Lyme disease is a tick-borne illness that can cause fatigue, sore

joints, and ultimately can damage the heart and nervous system. Most

cases are easily treated with

antibiotics. If not treated early in the infection, Lyme disease can

have lingering symptoms in about 10 percent of patients even after

treatment. The U.S. Centers for Disease Control and Prevention reports

17,730 U.S. cases of Lyme disease diagnosed in 2000, a record high. The

disease is concentrated in 12 northeastern states but was found in all

but six states in 2000, the most recent year for which statistics are

available.

At IBT, Sacchettini, Christoph Eicken, Ph.D., and Vivek Sharma, Ph.D.,

are managing a program to elucidate the structures of all outer surface

proteins that camouflage the Lyme disease bacterium (Borrelia

burgdorferi) and confuse the host immune system. " These structures

provide a roadmap to the development of new diagnostics as well as

effective vaccines, " Sacchettini said.

While understanding VlsE's structure has future research applications

for illuminating Lyme disease, it has more immediate utility as a

diagnostic tool, Norris said. More than 20 percent of Lyme disease

victims do not get a distinctive bulls-eye rash at the site of the tick

bite. Some victims simply fail to notice the rash.

Common lab tests that measure antibody responses to the entire Lyme

disease bacterium can be confounded by previous exposure to the disease

and cross-reactivity with other diseases. Using VlsE or a portion of the

protein in these tests gets around both of those problems, Norris has

found.

Norris' earlier research established the genetic structure of VlsE,

connected portions of the protein to Lyme disease's infectivity, and

described the antibody response

caused by the protein. UT-Houston co-authors include B. Lawrenz,

a graduate student in the UT-Houston Graduate School of Biomedical

Sciences, and M. Hardham, a former post-doctoral fellow in Norris'

lab.

The Texas A & M University System Health Science Center provides the state

with health education, outreach and research. Its five components,

located in communities throughout Texas, are Baylor College of

Dentistry, the College of Medicine, the Graduate School of Biomedical

Sciences, the Institute of Biosciences and Technology and the School of

Rural Public Health.

Source: News release from Texas A & M University System Health Science

Center